Clinical Trial Results:
A single arm phase II trial evaluating the activity of alectinib for the treatment of pretreated RET-rearranged advanced NSCLC
Summary
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EudraCT number |
2017-002063-17 |
Trial protocol |
ES BE NL SI IT |
Global end of trial date |
12 Oct 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Dec 2022
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First version publication date |
15 Dec 2022
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Other versions |
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Summary report(s) |
Statistical Analysis Plan |
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 |
ETOP12-17
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03445000 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Roche Number: MO30176 | ||
Sponsors
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Sponsor organisation name |
European Thoracic Oncology Platform
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Sponsor organisation address |
Effingerstr. 40, Bern, Switzerland, 3008
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Public contact |
ETOP Coordinating Office, ETOP, +41 31 511 94 00, regulatoryoffice@etop-eu.org
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Scientific contact |
ETOP Coordinating Office, ETOP, +41 31 511 94 00, regulatoryoffice@etop-eu.org
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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 |
Final
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Date of interim/final analysis |
12 Oct 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Mar 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Oct 2021
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To assess the efficacy of alectinib in terms of best overall response (OR) assessed by RECIST 1.1.
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Protection of trial subjects |
Alectinib is administered until progression, refusal or unacceptable toxicity. Trial treatment may also continue beyond progression, with physician and patient agreement, for as long as the patient may still derive clinical benefit as per investigator decision. The following events are closely monitored and represent selected AEs for this trial: abnormal renal function and acute kidney injury, anaemia, bradycardia, gastrointestinal effects, hepatotoxicity, interstitial lung disease (ILD) / pneumonitis, oedema, photosensitivity, rash, severe myalgia and CPK elevations, vision disorders. All AEs, regardless of relationship to IMP, are reported from the date of signature of informed consent until 30 days after the last dose of IMP. Management of adverse events may require dose reduction, temporary interruption, or discontinuation of treatment with alectinib. The dose of alectinib is reduced in steps of 150 mg twice daily based on tolerability. Alectinib treatment is permanently discontinued if patients are unable to tolerate the 300 mg twice daily dose. For women who are not postmenopausal (≥12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 3 months after the last dose of IMP. Men must agree to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 3 months after the last dose of IMP. Women who become pregnant while participating in the trial must discontinue trial medication immediately. The pregnancy is reported following procedures detailed in the protocol. Also, any pregnancy that occurs in a female partner of a male trial participant is reported.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Nov 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Netherlands: 6
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Country: Number of subjects enrolled |
Spain: 5
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Italy: 2
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Worldwide total number of subjects |
14
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EEA total number of subjects |
14
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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) |
10
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
Overall, 15 patients have been registered in the iBioBank from 6th of November 2018 until the 1st of April 2020, with 14 of them being enrolled, coming from centers in the Netherlands, Spain, Italy and Belgium. | ||||||||||||||||
Pre-assignment
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Screening details |
One patient was ineligible for enrolment due to active CNS metastases. | ||||||||||||||||
Period 1
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Period 1 title |
Overall trial period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
Arms
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Arm title
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Alectinib | ||||||||||||||||
Arm description |
Alectinib is administered orally, 600 mg, twice per day (1200 mg per day) until progression, refusal or unacceptable toxicity. Trial treatment may also continue beyond progression, with physician and patient agreement, for as long as the patient may still derive clinical benefit as per investigator decision. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Alectinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Alectinib is administered orally, 600 mg, twice per day (1200 mg per day) until progression, refusal or unacceptable toxicity. If a planned dose of alectinib is missed, patients can take the missed dose up until 6 hours before the next dose. Patients should not take two doses at the same time to make up for a missed dose. Alectinib treatment should be permanently discontinued if the treatment interruption exceeds 21 consecutive days. The appropriate number of alectinib capsules will be provided to patients to be self-administered at home. Patients will be asked to return the remaining trial medication at each treatment visit for a compliance check. The remaining capsules will be counted by the investigator/site staff and recorded at the investigator site. Discrepancies between the number of capsules remaining and the calculated number of capsules the patients should have taken as well as the information recorded in the patient diary must be documented and explained.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial period
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Reporting group description |
Intention-to-treat (ITT) population | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Alectinib
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Reporting group description |
Alectinib is administered orally, 600 mg, twice per day (1200 mg per day) until progression, refusal or unacceptable toxicity. Trial treatment may also continue beyond progression, with physician and patient agreement, for as long as the patient may still derive clinical benefit as per investigator decision. | ||
Subject analysis set title |
Efficacy cohort
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Efficacy cohort encompasses all evaluable patients, e.g. all enrolled patients excluding patients that were found to be ineligible (in retrospective review), patients that have never started the trial treatment and patients that are lost to follow-up before their first response evaluation (by RECIST 1.1). The efficacy cohort consists of 13 patients (there is one patient who was lost to follow-up before the first tumour assessment).
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Subject analysis set title |
Safety cohort
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety cohort includes all patients who received at least one dose of trial treatment (i.e. all 14 patients).
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End point title |
Best overall response (BOR) [1] | ||||||||||||||||||
End point description |
Best overall response (OR = CR or PR), per investigator assessment. OR was determined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). OR is defined as the best overall response [Complete Response (disappearance of all target and non-target lesions; no new lesions) or Partial Response (at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters; no new lesions)] across all assessment points. Radiological tumour assessments were performed using CT scans.
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End point type |
Primary
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End point timeframe |
Time from enrolment of the first patient until the database cut-off date for the primary BOR analysis (November 2018 - March 2021). The end of clinical follow-up of the last treated patient was in December 2020.
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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: Trial's accrual was terminated early, with only 13 patients consisting the efficacy cohort (of the total 41 required for the statistical test of proportions). |
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No statistical analyses for this end point |
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End point title |
Disease control at 24-weeks | ||||||||||
End point description |
Best overall response of CR or PR, or SD (or non-CR/non-PD in the case of non-measurable disease only).
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End point type |
Secondary
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End point timeframe |
Time from enrolment of the first patient until the database cut-off date for the primary BOR analysis (November 2018 - March 2021).
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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 |
Progression-free survival time is measured from the date of enrolment until documented progression or death, if progression is not documented. PFS is assessed according to RECIST 1.1 criteria.
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End point type |
Secondary
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End point timeframe |
Time from enrolment of the first patient until the database cut-off date for the primary BOR analysis (November 2018 - March 2021).
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No statistical analyses for this end point |
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End point title |
Overall survival (OS) | ||||||||
End point description |
Overall survival time is measured from the date of enrolment until death from any cause.
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End point type |
Secondary
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End point timeframe |
Time from enrolment of the first patient until the database cut-off date for the primary BOR analysis (November 2018 - March 2021).
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Notes [2] - 9999: Median survival time has not been reached; upper 95% confidence limit is not estimable. |
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No statistical analyses for this end point |
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End point title |
Safety and tolerability | ||||||||||
End point description |
The safety and tolerability of alectinib treatment is assessed through analysis of the worst grade of toxicity/adverse events according to CTCAE v4.0 criteria observed over the whole treatment period.
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End point type |
Secondary
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End point timeframe |
Time from treatment start of the first patient until the database cut-off date for the primary BOR analysis (November 2018 - March 2021).
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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 |
Adverse events were assessed from treatment start of the first patient until the database cut-off date for the primary BOR analysis (November 2018 - March 2021).
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Adverse event reporting additional description |
Safety and tolerability of alectinib treatment is assessed through analysis of the worst grade of toxicity/adverse events according to CTCAE v4.0 criteria observed over the whole treatment period.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
NCI CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
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Reporting groups
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Reporting group title |
Safety cohort
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Reporting group description |
The safety cohort will include all patients that have received at least one dose of trial treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||||||
Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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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. | |||||||
None reported | |||||||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/36030612 |