Clinical Trial Results:
An open-label, non-randomized, multicenter Phase I/II trial of RO5424802 given orally to non-small cell lung cancer patients who have ALK mutation and who have failed crizotinib treatment
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Summary
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EudraCT number |
2012-004455-36 |
Trial protocol |
SE GB DE IT ES NL BE FR DK LU |
Global end of trial date |
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Results information
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Results version number |
v1 |
This version publication date |
16 Mar 2016
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First version publication date |
16 Mar 2016
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
NP28673
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01801111 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, CH-4070, Basel, Switzerland,
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Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
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Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Interim
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Date of interim/final analysis |
29 Sep 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Aug 2014
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Global end of trial reached? |
No
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General information about the trial
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Main objective of the trial |
Part 1: To determine the recommended Phase II Dose (RP2D) of alectinib to be used in Phase II of the study and to assess the safety, tolerability, and pharmacokinetic (PK) of alectinib 600 milligrams (mg) twice daily (BID) and 900 mg twice daily (BID) (if reached) dose regimens.
Part 2 and Part 3: To evaluate efficacy by objective response rate (ORR) as per independent radiological review committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the overall population (with and without prior exposure of cytotoxic chemotherapy treatment[s]) and to evaluate efficacy by ORR as per IRC using RECIST version 1.1 in participants with prior exposure of cytotoxic chemotherapy treatment(s).
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Protection of trial subjects |
The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice (GCP) according to the regulations and procedures described in the protocol.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Jun 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Luxembourg: 2
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Country: Number of subjects enrolled |
Netherlands: 2
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Country: Number of subjects enrolled |
Russian Federation: 1
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Country: Number of subjects enrolled |
Singapore: 2
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Country: Number of subjects enrolled |
Spain: 7
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Country: Number of subjects enrolled |
Sweden: 5
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Country: Number of subjects enrolled |
Taiwan: 10
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Country: Number of subjects enrolled |
United Kingdom: 2
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Country: Number of subjects enrolled |
United States: 23
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Country: Number of subjects enrolled |
Australia: 7
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Denmark: 2
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Country: Number of subjects enrolled |
France: 32
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Country: Number of subjects enrolled |
Germany: 6
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Country: Number of subjects enrolled |
Italy: 19
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Country: Number of subjects enrolled |
Korea, Republic of: 17
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Worldwide total number of subjects |
138
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EEA total number of subjects |
78
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
124
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From 65 to 84 years |
14
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
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Pre-assignment
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Screening details |
Part 1 of study was planned to determine recommended Phase II Dose (RP2D) of alectinib to be used in Part 2. During the conduct of Part 1 for this study, RP2D was confirmed in Study NP28761 (NCT01871805). Hence Part 1 participants were merged into Part 2. Part 3 was post-progression treatment period. | ||||||||||||||
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Period 1
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Period 1 title |
Up to primary completion (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Alectinib | ||||||||||||||
Arm description |
Participants received alectinib 600 mg, capsule, orally, BID, continuously starting on Cycle 1 (28-day cycle), Day 1 until disease progression, death, or withdrawal for any other reasons. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Alectinib
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Investigational medicinal product code |
RO5424802
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Alectinib 600 mg BID within 30 minutes after meals in the morning and evening.
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Baseline characteristics reporting groups
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Reporting group title |
Alectinib
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Reporting group description |
Participants received alectinib 600 mg, capsule, orally, BID, continuously starting on Cycle 1 (28-day cycle), Day 1 until disease progression, death, or withdrawal for any other reasons. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Alectinib
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Reporting group description |
Participants received alectinib 600 mg, capsule, orally, BID, continuously starting on Cycle 1 (28-day cycle), Day 1 until disease progression, death, or withdrawal for any other reasons. | ||
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End point title |
Recommended Phase II Dose of Alectinib [1] | ||||||||
End point description |
RP2D was to be determined based on the safety and tolerability profile of the study treatment.
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End point type |
Primary
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End point timeframe |
Cycle 1 (up tp 28 days)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was not analysed. |
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| Notes [2] - The endpoint was not analyzed in this study as the RP2D was confirmed in study NP28761 (NCT01871805) |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Dose Limiting Toxicities (DLTs) [3] | ||||||||
End point description |
DLTs were to be assessed based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.3. DLTs: drug related toxicities that meet any one of the following criteria: Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade 4 neutropenia continuing for ≥ 7 consecutive days or neutropenic fever; nonhematological toxicity of Grade 3 or higher; adverse events that require interruption of treatment for a total of ≥7 days.
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End point type |
Primary
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End point timeframe |
Cycle 1 (up to 28 days)
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was not analysed. |
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| Notes [4] - The endpoint was not analyzed in this study as the RP2D was confirmed in study NP28761 (NCT018718) |
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Plasma Concentration Time Curve From Time 0 to 10 Hour Post-dose (AUC[0-10]) of Alectinib-Intensive PK Sampling [5] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 1 and Day 21 of Cycle 1
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was not analysed. |
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| Notes [6] - Data for this endpoint was not collected, as planned, because Part I of this study was not conducted |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Achieving Objective Response (Complete Response [CR] or Partial Response [PR]) as Assessed by Independent Radiological Review Committee (IRC) in Response Evaluable (RE) Population [7] | ||||||||
End point description |
Objective response was assessed by IRC according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size was <10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters). CR and PR was to be confirmed by repeat assessments ≥4 weeks after initial documentation. Analysis was performed on RE population (IRC): all participants with measurable disease at baseline according to the IRC, who had baseline tumor assessment and received at least one dose of alectinib.
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End point type |
Primary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical analysis was planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Pretreated Participants [8] | ||||||||
End point description |
Objective response was assessed by IRC according to RECIST version. 1.1. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size was <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters). CR and PR was to be confirmed by repeat assessments ≥4 weeks after initial documentation. Analysis was performed on RE population (IRC). Number of participants analyzed=participants from RE population (IRC) who received prior chemotherapy.
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End point type |
Primary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical analysis was planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Naive Participants | ||||||||
End point description |
Objective response was assessed by IRC according to RECIST version 1.1. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size was <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters). CR and PR was to be confirmed by repeat assessments ≥4 weeks after initial documentation. Analysis was performed on RE population (IRC). Number of participants analyzed=participants from RE population (IRC) who did not receive prior chemotherapy.
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End point type |
Secondary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Response Evaluable Population | ||||||||
End point description |
Objective response was assessed by investigator according to RECIST version. 1.1. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size was <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters). CR and PR was to be confirmed by repeat assessments ≥4 weeks after initial documentation. Analysis was performed on RE population (Investigator): all participants with measurable disease at baseline according to the investigator, who had baseline tumor assessment and received at least one dose of alectinib.
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End point type |
Secondary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Pretreated Participants | ||||||||
End point description |
Objective response was assessed by investigator according to RECIST version. 1.1. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size was <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters). CR and PR was to be confirmed by repeat assessments ≥4 weeks after initial documentation. Analysis was performed on RE population (investigator). Number of participants analyzed=participants from RE population (investigator) who received prior chemotherapy.
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End point type |
Secondary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Naive Participants | ||||||||
End point description |
Objective response was assessed by investigator according to RECIST version. 1.1. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size was <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters). CR and PR was to be confirmed by repeat assessments ≥4 weeks after initial documentation. Analysis was performed on RE population (investigator). Number of participants analyzed=participants from RE population (investigator) who did not receive prior chemotherapy.
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End point type |
Secondary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response | ||||||||||||||||
End point description |
Duration of response was defined as time from first observation of objective tumor response until first observation of disease progression using RECIST version 1.1 or death from any cause. Duration of response was estimated by Kaplan-Meier method and 95% CI was assessed using method of Brookmeyer and Crowley. Duration of response was assessed by IRC and by investigator as well as in subgroups of participants who received prior chemotharapy and who did not received prior chemotherapy. Here, "99999" and "-99999" represents data was not mature at the time of analysis as the study was ongoing. Analysis was performed on RE population: participants with measurable disease at baseline, had baseline tumor assessment and received at least one dose of alectinib. Number of participants analyzed= participants with measurable disease at baseline and had objective response. n=participants with measurable disease at baseline and had objective response for specified category.
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End point type |
Secondary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Percentage of Participants With Progression or Death | ||||||||||||||||
End point description |
Progression (according to RECIST version 1.1) was defined as at least a 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study or absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesion. Progression was assessed by IRC and by the investigator in safety population as well as in subgroups of participants who received prior chemotharapy and who did not received prior chemotherapy. Analysis was performed on Safety population.
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End point type |
Secondary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Percentage of Participants Who Died | ||||||||
End point description |
Analysis was performed on Safety population.
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End point type |
Secondary
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End point timeframe |
Baseline up to death or data cut off (18 August 2014, maximum follow up 53 weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression Free Survival (PFS) | ||||||||||||||||
End point description |
PFS was defined as the time interval between the date of the first treatment and the date of progression or death from any cause, whichever occurred first. Progression (according to RECIST version 1.1) was defined as at least a 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study or absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesion. Progression was assessed by IRC and by the investigator in safety population as well as in subgroups of participants who received prior chemotherapy and who did not received prior chemotherapy. PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley. Here "99999" represents data was not mature at the time of analysis as the study was ongoing. Analysis was performed on Safety population.
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End point type |
Secondary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Overall Survival (OS) | ||||||||
End point description |
OS was defined as the time from the date of first treatment to the date of death, regardless of the cause of death. OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley. Here "99999" represents data was not evaluable due to the short duration of follow-up at the time of the data cutoff. Analysis was performed on Safety population.
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End point type |
Secondary
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End point timeframe |
Baseline up to death or data cutoff (18 August 2014, maximum follow up 53 weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Achieving CR, PR or Stable Disease (SD, Lasting ≥16 Weeks) in Response Evaluable Population | ||||||||||||||||||||
End point description |
Disease control (CR, PR, or SD) was measured by RECIST version 1.1. by IRC and Investigator. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size is <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters). SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. Analysis was performed on RE population. Here, 'n' signifies participants with measurable disease at baseline for specified category.
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End point type |
Secondary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Duration of Response in Participants With CNS Response (CR or PR) as Assessed by IRC Based on RANO | ||||||||
End point description |
Duration of response in participants with CNS response was defined as time from 1st observation of CNS response (CR or PR) until 1st observation of CNS progression or death from any cause based on IRC review of radiographs by RANO criteria. Progression was defined by any of following: ≥ 25% increase in sum of products of diameters of measurable enhancing lesions compared to best response after initiation of therapy (nadir), or screening if screening was nadir value on stable or increasing doses of corticosteroids; significant increase in T2/FLAIR non-enhancing lesions not caused by co-morbid events on stable or increasing doses of corticosteroids; Any new lesions; Clear progression of enhancing non-measurable disease. Duration of response was estimated by Kaplan-Meier method and 95% CI was assessed using Brookmeyer and Crowley method. Clinical deterioration not attributable to other non-tumour causes. Participants with measurable CNS lesions at baseline according to IRC were included
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End point type |
Secondary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response in Participants With CNS Response (CR or PR) as Assessed by IRC Based on RECIST | ||||||||
End point description |
Duration of response in participants with CNS response was defined as time from first observation of CNS response (CR or PR) until first observation of CNS progression or death from any cause based on IRC review of radiographs by RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions. PR was defined as ≥30% decrease in sum of diameters of target lesions (taking as reference screening sum diameters) and no progression of target lesions. Progression was defined as ≥20% increase in sum of diameters of target lesions compared to smallest sum of diameters on-study or absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesion. Duration of response was estimated by Kaplan-Meier method and 95% CI was assessed using method of Brookmeyer and Crowley. Analysis was performed on Safety population. Number of participants analyzed=participants with measurable CNS lesions at baseline according to IRC.
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End point type |
Secondary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Achieving Objective Response (CR or PR) of Baseline Central Nervous System (CNS) Lesions As Assessed by IRC Based on Radiology Assessment in Neuro-Oncology (RANO) Criteria | ||||||||
End point description |
Objective response (CR and PR) of CNS lesions was assessed based on IRC review of radiographs by RANO criteria. CR was achieved if all of the following criteria met: Complete disappearance of all enhancing measurable and non-measurable disease; Stable or improved non-enhancing (T2/FLAIR) lesions; No new lesions; Participant must be off corticosteroids (or on physiologic replacement doses only), and clinically stable or improved. PR achieved if all of the following criteria met: at least 50% decrease compared with screening in SPD of measurable enhancing measurable lesions; No progression of non-measurable disease (enhancing and non-enhancing [T2/FLAIR] lesions); No new lesions; Participant must be off corticosteroids (or on physiologic replacement doses only), and clinically stable or improved. For both CR and PR, responses had to be sustained for at least 4 weeks. Safety population. Number of participants analyzed=participants with measurable CNS lesions at baseline according to IRC.
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End point type |
Secondary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Achieving Objective Response (CR or PR) of Baseline Central Nervous System (CNS) Lesions As Assessed by IRC Based on RECIST | ||||||||
End point description |
Objective response (CR and PR) of CNS lesions was assessed based on IRC review of radiographs by RECIST version 1.1 in participants with measurable CNS lesions at baseline. CR was defined as disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the screening sum diameters) and no progression of target lesions. Analysis was performed on Safety population. Number of participants analyzed=participants measurable CNS lesions at baseline and who achieved a CNS response of CR or PR according to IRC.
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End point type |
Secondary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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End point title |
Percentage of Participants With CNS Progression As Assessed by IRC Based on RECIST | ||||||||
End point description |
CNS progression was defined as the percentage of participants who developed a new CNS lesion or have disease progression in pre-existing CNS lesions based on IRC review of radiographs by RECIST version 1.1. Progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study or absolute increase of at lease 5 mm, progression of existing non-target lesions, or presence of new lesion. Analysis was performed on Safety population.
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End point type |
Secondary
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End point timeframe |
Baseline; assessments every 8 week post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up; data until cutoff (18 August 2014) are reported, maximum 53 weeks
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From Baseline to cut off (maximum 53 weeks of drug exposure)
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
Alectinib
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Reporting group description |
Participants received alectinib 600 mg, capsule, orally, BID, continuously starting on Cycle 1 (28 day cycle), Day 1 until disease progression, death, or withdrawal for any other reasons. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 Dec 2012 |
This purpose of this amendment was to remove exclusion criterion regarding use of anticoagulation or thrombolytic agent within 2 weeks prior to Day 1. |
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28 May 2013 |
To consolidate the country-specific Health Authorities’ requests that had been incorporated for Taiwan, Korea, Germany, France, United Kingdom, and Belgium.
Addition of total testosterone, free testosterone, follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) testing.
Removal of collection of sample for the Roche Clinical Repository.
Change in mandatory plasma sample collection: Addition of a completion/early termination sample.
Update on the reportable adverse events of special interest.
Update of the Schedule of Assessments, and PK/ECG schedule, in agreement with the changes made throughout the protocol. |
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19 Nov 2013 |
To modify specific inclusion and exclusion criteria for the midazolam sub study to allow enrolment of participants previously treated with any ALK inhibitor (approved or experimental).
To clarify the possibility of using parenteral formulations of midazolam for oral administration. |
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30 Jan 2014 |
To limit post-progression combination treatment (alectinib and erlotinib) in Part 3 of the study for participants with EGFR mutations to countries in which local health authorities and ethic committees permit it, following a request of the Spanish Health authority.
To remove the restriction for the last dose of crizotinib to be within 60 days from the first dose of alectinib. This restriction was first put in place to avoid possible re-sensitization to crizotinib and ensure that all participants are true crizotinib-failure. However, this limitation was thought to potentially affect enrollment as it may not have allowed enough time for participants to progress on subsequent chemotherapy treatments.
To update the permitted and prohibited medications based on the available drug drug interaction (DDI) information for alectinib with the intent to maintain the critical DDI restrictions to support appropriate use of alectinib for participants receiving concomitant medications
while ensuring patients were able to receive critical concomitant medications needed to treat comorbid conditions. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Part 1 analysis was not conducted as the during conduct of the study the RP2D was confirmed in study NP28761 (NCT01871805). | |||
