Clinical Trial Results:
NEO -ADJUVANT CHEMO/IMMUNOTHERAPY FOR THE TREATMENT OF RESECTABLE STAGE IIIA NON SMALL CELL LUNG CANCER (NSCLC): A PHASE II MULTICENTER EXPLORATORY STUD
|
Summary
|
|
EudraCT number |
2016-003732-20 |
Trial protocol |
ES |
Global end of trial date |
18 Oct 2023
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
30 Oct 2024
|
First version publication date |
30 Oct 2024
|
Other versions |
|
Summary report(s) |
Lancet Oncol article_NADIM |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
GECP16/03
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT03081689 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Fundación GECP
|
||
Sponsor organisation address |
Avda. Merididana 358, Barcelona, Spain, 08027
|
||
Public contact |
Eva Pereira, Fundación GECP, +34 934302006, epereira@gecp.org
|
||
Scientific contact |
Eva Pereira, Fundación GECP, +34 934302006, epereira@gecp.org
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
19 Mar 2024
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
18 Oct 2023
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
18 Oct 2023
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Estimate progression-free survival (PFS) at 24 months from diagnosis
|
||
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.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Feb 2017
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Spain: 46
|
||
Worldwide total number of subjects |
46
|
||
EEA total number of subjects |
46
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
44
|
||
From 65 to 84 years |
2
|
||
85 years and over |
0
|
||
|
|||||||
|
Recruitment
|
|||||||
Recruitment details |
Between April 26, 2017, and Aug 25, 2018, we screened 51 patients for eligibility, of whom 46 patients were enrolled from 25 different sites and received neoadjuvant treatment. | ||||||
|
Pre-assignment
|
|||||||
Screening details |
Screening details: Patients eligible for the trial are those with a histological diagnosis or cytologically proven operable and resectable non-small-cell lung cancer, stage IIIA. | ||||||
|
Period 1
|
|||||||
Period 1 title |
Overall study (overall period)
|
||||||
Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
|
||||||
Blinding used |
Not blinded | ||||||
|
Arms
|
|||||||
|
Arm title
|
Experimental | ||||||
Arm description |
Patients received the following drugs intravenously, as neoadjuvant treatment: nivolumab (360 mg), paclitaxel (200 mg/m²), and carboplatin (area under the curve 6; 6 mg/mL per min), on day 1 of each 21-day cycle, for three cycles before surgical resection. After completion of neoadjuvant chemoimmunotherapy, surgery was planned 42–49 days after the first day of the third treatment cycle. Resection of the primary tumour and lymph nodes was done according to standard institutional procedures. Once the patients were deemed fully recovered from surgery, adjuvant treatment with nivolumab was scheduled to commence 3–8 weeks after surgery. Patients received intravenous nivolumab as adjuvant treatment at a fixed dose of 240 mg every 2 weeks for 4 months, followed by a fixed dose of 480 mg every 4 weeks, until month 12. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Nivolumab
|
||||||
Investigational medicinal product code |
BMS-936558 or MDX1106
|
||||||
Other name |
Opdivo
|
||||||
Pharmaceutical forms |
Solution for infusion
|
||||||
Routes of administration |
Intravenous use
|
||||||
Dosage and administration details |
- Neoadjuvant treatment: Nivolumab 360 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W, 3 cycles
- Surgery
- Adjuvant treatment: Nivolumab 240 mg Q2W for 4 months and Nivolumab 480 mg Q4W for 8 months (1 year) after surgical resection
Dose reductions were not permitted for nivolumab; however, nivolumab treatment could be interrupted, delayed, or discontinued depending on tolerability
|
||||||
|
|||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall study (overall period)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Experimental
|
||
Reporting group description |
Patients received the following drugs intravenously, as neoadjuvant treatment: nivolumab (360 mg), paclitaxel (200 mg/m²), and carboplatin (area under the curve 6; 6 mg/mL per min), on day 1 of each 21-day cycle, for three cycles before surgical resection. After completion of neoadjuvant chemoimmunotherapy, surgery was planned 42–49 days after the first day of the third treatment cycle. Resection of the primary tumour and lymph nodes was done according to standard institutional procedures. Once the patients were deemed fully recovered from surgery, adjuvant treatment with nivolumab was scheduled to commence 3–8 weeks after surgery. Patients received intravenous nivolumab as adjuvant treatment at a fixed dose of 240 mg every 2 weeks for 4 months, followed by a fixed dose of 480 mg every 4 weeks, until month 12. | ||
|
|||||||||
End point title |
Progression Free Survival at 24 months [1] | ||||||||
End point description |
Rate of PFS at 24 months from diagnosis defined as the rate of patients free of disease progression or death from any cause whichever occurs first as determined by the investigator according to RECIST v1.1. criteria for systemic disease.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
At 24 months from diagnosis
|
||||||||
| 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: Progression-free survival, compared with that reported for these patients in previous studies (ranging from 40% in patients receiving standard therapy, considered here as the null hypothesis, to 55% in patients receiving the analysed treatment),15–17 with a one-sided type I error of 5%. We used the Kaplan-Meier method to estimate progression-free survival and overall survival and corresponding 95% CIs. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall Survival | ||||||||
End point description |
Percentage of patients are still alive
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
At 3 years from the first dose of neoadjuvant treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 dose study treatment administration.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
As-treated population
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
22 Jun 2017 |
New protocol version: Modify the version of TNM required for staging patients from TNM 7th edition to TNM 8th editing and clarify schedule of study procedures |
||
09 May 2018 |
New version of protocol: Add the option to replace invalid patients to complete the patient sample initially calculated in order to meet the initially set statistical objectives and clarify an inclusion criterion in relation to the version of the TNM accepted by protocol |
||
15 Jan 2019 |
Change of Sponsor of study |
||
20 Jun 2019 |
Changes in the protocol: The information contained in the protocol is reviewed regarding the pharmacogenetic analyzes to be performed on the samples extracted from the patients included in the study. A more detailed description of said analyzes and the objectives that are intended to be met with said analyzes is made.
|
||
16 Nov 2020 |
Changes in the protocol: The information contained in the protocol is reviewed regarding the analyzes to be performed on the computed tomography (CT) scans of the patients included in the study. A new analysis is added that can contribute to better understanding the clinical evolution of patients with lung cancer by obtaining predictions of the results of possible treatments.
|
||
22 Sep 2022 |
Changes in the protocol: The follow-up period of the NADIM study was planned to last 3 years and will be extended to 5 years. The analysis of these 2 additional years may contribute to better understanding the clinical evolution of patients with lung cancer.
|
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
|||
| http://www.ncbi.nlm.nih.gov/pubmed/35576508 http://www.ncbi.nlm.nih.gov/pubmed/32979984 |
|||
