Clinical Trial Results:
Phase II clinical trial with tri-weekly metronomic oral vinorelbine and cisplatin as induction treatment for and subsequent concomitant with radiotherapy (RT) in patients with non small cell lung cancer (NSCLC) locally advanced unresectable.
Summary
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EudraCT number |
2015-003312-21 |
Trial protocol |
ES |
Global end of trial date |
20 Dec 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Feb 2021
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First version publication date |
03 Feb 2021
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Other versions |
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Summary report(s) |
GECP_NORA_final report_summary |
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 |
GECP15/02_NORA
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02709720 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Grupo Español de Cáncer de Pulmón
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Sponsor organisation address |
Avenida Meridiana 358, 6ª planta, Barcelona, Spain, 08027
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Public contact |
Eva Pereira Álvarez, Grupo Español de Cáncer de Pulmón, 34 934302006, epereira@gecp.org
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Scientific contact |
Mariano Provencio, Grupo Español de Cáncer de Pulmón, 34 934302006, epereira@gecp.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 |
19 May 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Dec 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Dec 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy in terms of progression-free survival (PFS) of oral metronomic vinorelbine and cisplatin as an induction treatment and posteriorly with concomitant radiotherapy.
The PFS is defined as the time since the randomization until the progression documentation or exitus for any reason ( any death with or without evidence of progression, will be considered events on the exitus date and these that will not progress in the moment of the analysis will be censored with the date of the last control).
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Apr 2016
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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 |
Spain: 65
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Worldwide total number of subjects |
65
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EEA total number of subjects |
65
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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) |
45
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From 65 to 84 years |
20
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85 years and over |
0
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Recruitment
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Recruitment details |
Initially, 68 patients were recruited in 18 centers between April 2016 and June 2017. Although one of them was excluded after not meeting the first inclusion criteria, another for not being able to start treatment and another because their treatment did not follow the protocol. Finally 65 patients were finally selected for final analysis | ||||||
Pre-assignment
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Screening details |
The study selected patients diagnosed with locally advanced NSCLC who had not performed no prior cytostatic, radiotherapy or surgical treatment for the disease. | ||||||
Period 1
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Period 1 title |
Overall study (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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Arm of study | ||||||
Arm description |
2 cycles of metronomic Vinorelbine 50 mg + cisplatin 80mg/m2, followed by 2 cycles of Vinorelbine 30 mg + cisplatin 80mg/m2 concomitant with radiotherapy | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Vinorelbine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, soft
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Routes of administration |
Oral use
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Dosage and administration details |
Induction chemotherapy:
Metronomic oral vinorelbine: 50mg / day, on Monday, Wednesday and Friday of each week, for 2 cycles.
1 cycle equals 21 days (9 administrations of oral vinorelbine).
Concomitant chemotherapy with radiation therapy:
Metronomic oral vinorelbine: 30mg / day, on Monday, Wednesday and Friday of each week, for 2 cycles.
1 cycle equals 21 days (9 administrations of oral vinorelbine).
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Investigational medicinal product name |
Cisplatin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Induction chemotherapy:
Cisplatin: 80 mg / m2 day 1 every 21 days, for 2 cycles.
1 cycle equals 21 days (1 administration of cisplatin).
Concomitant chemotherapy with radiation therapy:
Cisplatin: 80 mg / m2 day 1 every 21 days, for 2 cycles.
1 cycle equals 21 days (1 administration of cisplatin).
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Baseline characteristics reporting groups
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Reporting group title |
Overall study (overall period)
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Reporting group description |
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End points reporting groups
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Reporting group title |
Arm of study
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Reporting group description |
2 cycles of metronomic Vinorelbine 50 mg + cisplatin 80mg/m2, followed by 2 cycles of Vinorelbine 30 mg + cisplatin 80mg/m2 concomitant with radiotherapy |
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End point title |
Progression-free Survival [1] | ||||||||
End point description |
To assess the efficacy in terms of progression-free survival (PFS) of oral metronomic vinorelbine and cisplatin as induction therapy and then with concomitant radiotherapy. PFS is defined as the time from the moment of inclusion of the patient to documentation of progression or death from any cause (that is, patients who die without evidence of progression will be considered events on the date of death and those that have not progressed at the time of the analysis will be censored with the date of the last control).
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End point type |
Primary
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End point timeframe |
At the end of study
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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: The estimated median progression-free survival (PFS) was 11.5 months (95% CI 9.6-15.4), with an estimated PFS of 79.6% (95% CI 67.5-87.6%) at 6 months, 47.8% (95% CI 35.1-59.4%) at 12 months and 25.5% (15.5-36.6%) at 24 months. The NORA study provides a new concept to explore with the use of metronomic chemotherapy. The studied treatment achieves an estimated median PFS of 11.5 m and 47.8% (95% CI 35.1-59.4%) at 12 months, which in the case of the PACIFIC study is 16.8 m and 55 per year resp. |
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No statistical analyses for this end point |
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End point title |
Overall survival | ||||||||
End point description |
Overall survival was measured from the date of inclusion of the patient until death or loss to follow-up. In patients who have not died, the duration of survival will be censored on the date of the last contact if the patient causes loss to follow-up or on the date of the latest news.
Survival curves for overall survival have been estimated using the Kaplan-Meier method, obtaining estimates for the measures and survival rates at different times with their corresponding confidence intervals with a confidence level of 95%, using the adequate procedures for estimating these intervals.
We have an estimated median overall survival of 35.6 months (95% CI 24.4-46.8 months), with an estimated survival of 93.7% at 6 months (95% CI 84.1-97.6%) , 81.0% at 12 months (95% CI 69.0-88.7%) and 60.4% at 24 months (95% CI 47.2-71.2%).
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End point type |
Secondary
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End point timeframe |
At the end of study
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No statistical analyses for this end point |
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End point title |
Objective tumor response | ||||||||||||||||
End point description |
Objective response rate of the treatment, by assessing the target lesions according to the RECIST criteria (version 1.1).
Objective response analyses was estimated using the Kaplan-Meier method with a confidence level of 95%, using the appropriate procedures.
The best response to treatment of these 65 patients is described, with 4 patients (6.2%) presenting a complete response (95% CI 2.4-14.8%), 39 (60.0%) presenting a partial response (95% CI 47.9-71.0%), 12 (18.5%) with stable disease (95% CI 10.9-29.6%), 7 with progression (10.8%) (95% CI 5.3 -20.6%) and 3 in which the response could not be evaluated (4.6%) (95% CI 1.6-12.7%). We can see that, of the 51 patients who have completed treatment, 4 (7.8%) present a CR, 36 (70.6%) a PD and 11 (21,6%) SD. We also have 14 patients who have not completed treatment, of which 3 (21.4%) presented partial response, 1 (7.1%) stable disease, 7 (50.0%) progression and 3 (21.4%) not evaluable.
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End point type |
Secondary
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End point timeframe |
At the end of study
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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 |
Any adverse event or breakdown occurring during the course of the study.
The investigator will have to collect all adverse events once they have signed informed consent, during treatment and 30 days after the last
administration of the study.
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Adverse event reporting additional description |
The severity of AE will be determined using CTCAE version 4.0.
Consistent with EudraCT disclosure specifications, GECP has reported under the SAE field “number of deaths resulting from AE” 0 deaths, because there are not deemed to be causally related to treatment by the investigator. In total were 9 exitus.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.1
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Reporting groups
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Reporting group title |
Subjects per protocol
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Reporting group description |
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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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06 Feb 2017 |
Correct the total number of patients and sites in the study after the statistical review of the analysis initially proposed. |
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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. | |||
Not applicable. |