Back to resultsIntegrative Analysis of the Tumor Microenvironment and Optimization of the Immunotherapy Duration in Non-small Cell Lung Cancer Patients. (OPTIMUNE-LUNG)
Primary Purpose
Non Small Cell Lung Cancer
Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
ICI treatment discontinuation
ICI treatment continuation
Sponsored by
About this trial
This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring Immune checkpoint inhibition, non-small cell lung cancer, treatment duration, long-term benefit
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed non-small cell lung carcinoma (squamous or non squamous).
- Locally advanced/unresectable or metastatic disease.
- For non-squamous histology, tumor with no oncogenic addiction: no activating EGFR mutation, no ALK or ROS1 rearrangement,
Treatment with ICI (immune checkpoint inhibitor PD1/PDL-1 blockade therapy):
- in first or second-line treatment as per market authorization. For patients in first line, ICI alone or ICI + chemotherapy,
- start of ICI treatment 6 to 12 months (+/- 2 weeks) before registration.
- At least one measurable lesion according to the RECIST v1.1 criteria before ICI treatment onset and confirmed by centralized review (lesion in previously irradiated filed can be considered as measurable if progressive at inclusion according to RECIST v1.1). At least one site of disease must be uni-dimensionally ≥ 10 mm.
- Patient with objective response according to RECIST v1.1 criteria at 6 months or more and less than 12 months after ICI treatment onset. Response must be confirmed by centralized review
- At least one lesion that can be biopsied for research purpose.
- Age ≥ 18.
- Performance status < 2.
- Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration.
- Patient with a social security in compliance with the French law (Loi Jardé).
- Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
- Voluntarily signed and dated written informed consent prior to any study specific procedure.
Exclusion Criteria:
- Female who is pregnant or breast-feeding.
- Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.
- Hypersensitivity to one of the active substances or to one of the excipients
- Any contraindication to pursue ICI treatment as per investigator judgement.
- Previous enrolment in the present study.
- Individual deprived of liberty or placed under legal guardianship.
Sites / Locations
- Centre Hospitalier de la Côte Basque
- Clinique Tivoli Ducos
- Institut BergonieRecruiting
- Polyclinique Bordeaux Nord Aquitaine
- Clinique Marzet
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Experimental
Arm Label
Standard Arm A: treatment by ICI will be continued
Experimental Arm B: treatment by ICI will be discontinued
Arm Description
After achieving objective response between 6 and 12 months after treatment onset, for these patients ICI treament will continue as per market authorization
After achieving objective response between 6 and 12 months after treatment onset, for these patients first-line or second line regimen should be discontinued. Patients will be followed as per standard management.
Outcomes
Primary Outcome Measures
Assessment of the long-term benefit of PD-1 inhibition in NSCLC patients who experienced a response between 6 and 12 months after initiation of ICI
Long-term benefit will be assessed in terms of progression-free rate (PFR) at 12 months after randomization, for each therapeutic strategy
Secondary Outcome Measures
Assessment of secondary resistance in NSCLC patients who experienced a response to PD1/PDL-1 inhibition
The rate of patients who develop progression (as per RECIST v1.1) due to secondary resistance after obtaining a response to PD1/PDL-1 inhibition, independently for each therapeutic strategy
Duration of response independently for each therapeutic strategy
Duration of response (DoR) defined as the time interval between the first response (complete or partial response as per RECIST v1.1) to the time of the first documentation of disease progression
1-year progression-free survival, independently for each therapeutic strategy
Progression-free survival (PFS) defined as the time interval between the date of randomization and the date of progression or death, whichever occurs first. Progression will be determined according to RECIST v1.1
2-year progression-free survival, independently for each therapeutic strategy
Progression-free survival (PFS) defined as the time interval between the date of randomization and the date of progression or death, whichever occurs first. Progression will be determined according to RECIST v1.1
1-year overall survival, independently for each therapeutic strategy
Overall Survival (OS) defined as the time interval between the date of randomization and the date of death (of any cause)
2-year overall survival, independently for each therapeutic strategy
Overall Survival (OS) defined as the time interval between the date of randomization and the date of death (of any cause)
Safety profile, independently for each therapeutic strategy: Common Terminology Criteria for Adverse Events version 5
Toxicity graded using the Common Terminology Criteria for Adverse Events version 5
• To describe retreatment for arm B-patients and subsequent systemic therapies for arm A-patients
Number of patients retreated by ICI will be described in Arm B. Similarly, for arm A-patients, number of patients treated by subsequent systemic therapy will be described
Tumor immune cells levels
Levels of immune cells in tumor will be measured by immunohistochemistry.
Blood cytokines levels
Levels of cytokines in blood will be measured by ELISA
Blood lymphocytes levels
Levels of lymphocytes in blood will be measured by flow cytometry
Blood kynurenine levels
Levels of kynurenine in blood will be measured by ELISA
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04880382
Brief Title
Integrative Analysis of the Tumor Microenvironment and Optimization of the Immunotherapy Duration in Non-small Cell Lung Cancer Patients.
Acronym
OPTIMUNE-LUNG
Official Title
Integrative Analysis of the Tumor Microenvironment and Optimization of the Immunotherapy Duration in Non-small Cell Lung Cancer Patients. OPTIMUNE-LUNG Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 27, 2021 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Bergonié
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Non-comparative multicentric randomized study to assess long-term benefit of PD-1 inhibition in NSCLC patients who experienced a response between 6 and 12 months after initiation of ICI (immune checkpoint inhibitor PD1/PDL-1 blockade therapy)
Detailed Description
Two-arm, non-comparative, prospective, multicentric, randomized study for early discontinuation of immune checkpoint inhibitor PD1/PDL-1 blockade therapy in non-small cell lung cancer patients who achieved objective response between 6 and 12 months after treatment onset.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer
Keywords
Immune checkpoint inhibition, non-small cell lung cancer, treatment duration, long-term benefit
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized phase II study in which eligible patients will be randomized (1:1) according to two therapeutic strategies
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Standard Arm A: treatment by ICI will be continued
Arm Type
Other
Arm Description
After achieving objective response between 6 and 12 months after treatment onset, for these patients ICI treament will continue as per market authorization
Arm Title
Experimental Arm B: treatment by ICI will be discontinued
Arm Type
Experimental
Arm Description
After achieving objective response between 6 and 12 months after treatment onset, for these patients first-line or second line regimen should be discontinued. Patients will be followed as per standard management.
Intervention Type
Drug
Intervention Name(s)
ICI treatment discontinuation
Intervention Description
After achieving objective response between 6 and 12 months after treatment onset, for these patients, first or second line treatment by immune checkpoint inhibitor will be discontinued. Patients will be followed as per standard mangement thereafter
Intervention Type
Drug
Intervention Name(s)
ICI treatment continuation
Intervention Description
After achieving objective response between 6 and 12 months after treatment onset, for these patients, first or second line treatment by immune checkpoint inhibitor will be continued until disease progreession or unacceptable toxicity
Primary Outcome Measure Information:
Title
Assessment of the long-term benefit of PD-1 inhibition in NSCLC patients who experienced a response between 6 and 12 months after initiation of ICI
Description
Long-term benefit will be assessed in terms of progression-free rate (PFR) at 12 months after randomization, for each therapeutic strategy
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Assessment of secondary resistance in NSCLC patients who experienced a response to PD1/PDL-1 inhibition
Description
The rate of patients who develop progression (as per RECIST v1.1) due to secondary resistance after obtaining a response to PD1/PDL-1 inhibition, independently for each therapeutic strategy
Time Frame
12 months
Title
Duration of response independently for each therapeutic strategy
Description
Duration of response (DoR) defined as the time interval between the first response (complete or partial response as per RECIST v1.1) to the time of the first documentation of disease progression
Time Frame
Throughout the treatment period, an expected average of 12 months
Title
1-year progression-free survival, independently for each therapeutic strategy
Description
Progression-free survival (PFS) defined as the time interval between the date of randomization and the date of progression or death, whichever occurs first. Progression will be determined according to RECIST v1.1
Time Frame
1 year
Title
2-year progression-free survival, independently for each therapeutic strategy
Description
Progression-free survival (PFS) defined as the time interval between the date of randomization and the date of progression or death, whichever occurs first. Progression will be determined according to RECIST v1.1
Time Frame
2 years
Title
1-year overall survival, independently for each therapeutic strategy
Description
Overall Survival (OS) defined as the time interval between the date of randomization and the date of death (of any cause)
Time Frame
1 year
Title
2-year overall survival, independently for each therapeutic strategy
Description
Overall Survival (OS) defined as the time interval between the date of randomization and the date of death (of any cause)
Time Frame
2 years
Title
Safety profile, independently for each therapeutic strategy: Common Terminology Criteria for Adverse Events version 5
Description
Toxicity graded using the Common Terminology Criteria for Adverse Events version 5
Time Frame
Throughout the treatment and follow-up period, an expected average of 12 months
Title
• To describe retreatment for arm B-patients and subsequent systemic therapies for arm A-patients
Description
Number of patients retreated by ICI will be described in Arm B. Similarly, for arm A-patients, number of patients treated by subsequent systemic therapy will be described
Time Frame
Throughout the treatment and follow-up period, an expected average of 12 months
Title
Tumor immune cells levels
Description
Levels of immune cells in tumor will be measured by immunohistochemistry.
Time Frame
At study onset (randomization) and at progression (throughout the treatment and follow-up period, an average of 12 months)
Title
Blood cytokines levels
Description
Levels of cytokines in blood will be measured by ELISA
Time Frame
At study onset (randomization) and at progression (throughout the treatment and follow-up period, an average of 12 months)
Title
Blood lymphocytes levels
Description
Levels of lymphocytes in blood will be measured by flow cytometry
Time Frame
At study onset (randomization) and at progression (throughout the treatment and follow-up period, an average of 12 months)
Title
Blood kynurenine levels
Description
Levels of kynurenine in blood will be measured by ELISA
Time Frame
At study onset (randomization) and at progression (throughout the treatment and follow-up period, an average of 12 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed non-small cell lung carcinoma (squamous or non squamous).
Locally advanced/unresectable or metastatic disease.
For non-squamous histology, tumor with no oncogenic addiction: no activating EGFR mutation, no ALK or ROS1 rearrangement,
Treatment with ICI (immune checkpoint inhibitor PD1/PDL-1 blockade therapy):
in first or second-line treatment as per market authorization. For patients in first line, ICI alone or ICI + chemotherapy,
start of ICI treatment 6 to 12 months (+/- 2 weeks) before registration.
At least one measurable lesion according to the RECIST v1.1 criteria before ICI treatment onset and confirmed by centralized review (lesion in previously irradiated filed can be considered as measurable if progressive at inclusion according to RECIST v1.1). At least one site of disease must be uni-dimensionally ≥ 10 mm.
Patient with objective response according to RECIST v1.1 criteria at 6 months or more and less than 12 months after ICI treatment onset. Response must be confirmed by centralized review
At least one lesion that can be biopsied for research purpose.
Age ≥ 18.
Performance status < 2.
Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration.
Patient with a social security in compliance with the French law (Loi Jardé).
Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Voluntarily signed and dated written informed consent prior to any study specific procedure.
Exclusion Criteria:
Female who is pregnant or breast-feeding.
Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.
Hypersensitivity to one of the active substances or to one of the excipients
Any contraindication to pursue ICI treatment as per investigator judgement.
Previous enrolment in the present study.
Individual deprived of liberty or placed under legal guardianship.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sophie COUSIN, MD
Phone
5.56.33.33.33
Ext
+33
Email
s.cousin@bordeaux.unicancer.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Simone MATHOULIN-PELISSIER, MD, PhD
Email
s.mathoulin@bordeaux.unicancer.fr
Facility Information:
Facility Name
Centre Hospitalier de la Côte Basque
City
Bayonne
ZIP/Postal Code
64109
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marielle SABATINI, MD
Email
msabatini@ch-cotebasque.fr
Facility Name
Clinique Tivoli Ducos
City
Bordeaux
ZIP/Postal Code
33000
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valérie Cochin, MD
Email
v.cochin@clinique-tivoli.com
Facility Name
Institut Bergonie
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sophie COUSIN, MD
Email
s.cousin@bordeaux.unicancer.fr
First Name & Middle Initial & Last Name & Degree
Sophie COUSIN, MD
Facility Name
Polyclinique Bordeaux Nord Aquitaine
City
Bordeaux
ZIP/Postal Code
33077
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Camille Mazza, MD
Email
c.mazza@bordeauxnord.com
Facility Name
Clinique Marzet
City
Pau
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sylvestre LE MOULEC, MD
Email
sylvestre.lemoulec@gmail.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Integrative Analysis of the Tumor Microenvironment and Optimization of the Immunotherapy Duration in Non-small Cell Lung Cancer Patients.
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