Trial assessing treatment in patients with advanced Lung Cancer and Interstitial Lung Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intergroupe Francophone De Cancerologie Thoracique

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-04-17

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

IFCT

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

1rst line : Efficacy of carboplatine and weekly paclitaxel +/- bevacizumab for advanced NSCLC patients with ILD.
2nd line : Assessment of respiratory toxicity of treatment in ARM A (best investigator choice chemotherapy) and in ARM B (i.e of pembrolizumab or nivolumab) as second-line treatment for advanced NSCLC patients with non-severe ILD.

Secondary objectives 6

1. Evaluation of the efficacy of treatments.
2. Evaluation of the efficacy of treatments according to ILDs pattern on CT scan and severity.
3. Impact of anti-fibrosing treatments on efficacy and respiratory evolution.
4. Evaluation of the Quality of life.
5. Evaluation of the safety of treatments
6. Immune-related toxicities (2nd line only)

Conditions and MedDRA coding

Non Small Cell Lung Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Informed, written and signed consent: Patients must have signed and dated the written informed consent form approved by the ethics committee in accordance with the legal and institutional framework. It must have been signed before protocol-related procedures that are not part of normal patient management are performed. Patients should be willing and able to adhere to the schedule of visits, treatment and laboratory tests.
2. For female patients of childbearing potential and patients with a partner of childbearing potential, agreement (by the patient and/or partner) to use one or more highly effective contraceptives (failure rate < 1% per year when used correctly and regularly) and to continue using it for 7 months after the last dose of treatment. Men should not donate their sperm for the duration of the study and for at least 7 months after the last dose of treatment. Oral contraception should always be combined with another method of contraception because of potential interactions with treatment. Patients should always use a condom.
3. Patient covered by national health insurance.
4. Protected adults may participate in the study if they can make decisions regarding their medical treatment in accordance with the guardianship judgment
5. Patients with radiological ILDs. All cases should be presented in a multidisciplinary board dedicated to ILD to confirm eligibility. In centres without a local multidisciplinary board dedicated to ILD, the national multidisciplinary board CAPID can be used.
6. NSCLC proven histologically. Cytological evidence is allowed if a cytoblock has been prepared.
7. Age ≥ 18 years old.
8. Performance status ≤ 2.
9. Stage IIIB or IIIC non-irradiable/non-irradiated or IV (8th TNM classification, UICC 2015). For other less advanced stages but rejected for any local treatment, possible inclusion discussion with the sponsor
10. Disease measurable according to RECIST criteria 1.1 per investigator assessment.
11. Adequate biological function: Creatinine clearance ≥ 45 mL/min (Cockroft or MDRD or CKD-epi); neutrophils ≥ 1500/mm3; platelets ≥ 100,000/mm3; Haemoglobin ≥ 9 g/dL; liver enzymes< 3x UNL except for patients with liver metastases (< 5x UNL); total bilirubin ≤ 1.5x UNL except for patients with proven Gilbert's syndrome (≤ 5x UNL) or patients with liver metastases (≤ 3.0 mg/dL).
12. Life expectancy of at least 12 weeks.
13. 1st line only:Patient must be treatment naive for advanced or metastatic disease. Treatment for non-metastatic stage is not considered as a line if there is a time interval of at least 6 months between the last dose of treatment for non-metastatic stage and recurrent disease.
14. 1st line only: ILD criteria: any type of ILD and any level of severity are allowed
15. 2nd line only: Patients must have received one but no more than one platinum-based therapy for advanced or metastatic disease. Treatment for non-metastatic stage is not considered as a line if there is a time interval of at least 6 months between the last dose of treatment for non-metastatic stage and recurrent disease.
16. 2nd line only:ILD severity criteria: Patients with ILDs with mild to moderate alteration of pulmonary function, defined by Forced Vital Capacity (FVC) ≥ 50% of the predicted value AND DLCO≥ 35% of the of the predicted value. All cases should be presented in a multidisciplinary board dedicated to ILD to confirm eligibility. In centers without a local multidisciplinary board dedicated to ILD, the national multidisciplinary board CAPID can be used.
17. 2nd line only: ILD type criteria: Patient with idiopathic interstitial pneumonia (including IPF and NSIP) or secondary ILDs (including hypersensitivity pneumonia, pneumoconiosis, radiation pneumonitis) could be included. Will be excluded patients with ILDs secondary to connective tissue disease, vasculitis or granulomatosis (including but not limited to granulomatosis with polyangiitis, rheumatoid arthritis, Sjogren's syndrome, scleroderma, myositis/dermatomyositis, anti-synthetase syndrome). For sarcoidosis and for Interstitial pneumonia with autoimmune features (IPAF) inclusion could be confirmed based on a case-by-case discussion with the sponsor.
18. 2nd line only: Available results for Immunoassay including antinuclear antibodies tested by immunofluorescence, rheumatoid factor, anti-CCP, Anti-dsDNA, Anti-Ro (SS-A), Anti-La (SS-B), Anti-ribonucleoprotein, Anti-Smith, Anti-topoisomerase (Scl-70), Anti-tRNA synthetase (Jo-1, PL-7, PL-12, Anti-PM-Scl, Anti-MDA-5), ANCA.

Exclusion criteria 14

1. Small cell cancer or tumor with mixed histology including a small cell component.
2. 2nd line only : Corticosteroid therapy > 10 mg daily oral prednisone or equivalent.
3. 2nd line only : Immunosuppressive therapy within two weeks prior to randomization.
4. Known EGFR activating mutation (deletion LREA in exon 19, mutation L858R or L861X in exon 21, mutation G719A/S in exon 18). Known rearrangement of ALK or ROS1 genes evaluated by immunohistochemistry, FISH or NGS sequencing.
5. History of cancer or cancer active within 3 years except those with a negligible risk of metastasis or death treated curatively (such as adequately treated cervical cancer in situ, basal or squamous cell skin cancer or ductal carcinoma in situ curatively treated. For other types of cancer, please contact the IFCT). Patients with a history of prostate cancer in the last 5 years may be included in cases of localized prostate cancer of good prognosis according to the Amico classification (≤ T2a and Gleason score ≤ 6 and PSA ≤ 10 ng/mL) and if they have been treated curatively (surgery or radiotherapy ± hormone therapy, without chemotherapy).
6. Acute exacerbation of interstitial lung disease less than 6 months ago.
7. 1rst line only : Previous systemic therapy (including but not limited to chemotherapy, targeted therapy, immunotherapy) except for adjuvant therapies given more than 5 years ago
8. 2nd line only : History of severe allergy, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the pembrolizumab/nivolumab formulation.
9. 2nd line only : Diagnosis of interstitial lung disease with manifestations of autoimmunity (IPAF) according to ATS/ERS criteria
10. 2nd line only : History of autoimmune disease, connective tissue disease, vasculitis or granulomatosis associated with but not limited to myasthenia gravis, myositis, autoimmune hepatitis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis.
11. 2nd line only : Diagnosis of ILDs due to connective tissue disease, vasculitis or granulomatosis including but not limited to granulomatosis with polyangiitis, rheumatoid arthritis, Sjogren's syndrome, scleroderma, myositis/dermatomyositis, anti-synthetase syndrome. For sarcoidosis and for Interstitial pneumonia with autoimmune features (IPAF) inclusion could be confirmed based on a case-by-case discussion with the sponsor.
12. 2nd line only: More than one line of treatment
13. 2nd line only: any prior Immunotherapy
14. 2nd line only: Patients who have had major surgery ≤ 3 weeks before randomization.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1rst line : The primary endpoint is Disease control rate define by the % of patient with a stable (SD), partial response (PR) or complete response (CR) on CT scanner evaluation at 8 weeks assessed by investigators according to RECIST 1.1.
2. 2nd line : The primary outcome is the treatment related respiratory worsening leading to discontinuation of treatment during the first 6 months

Secondary endpoints 10

1. Progression-free survival
2. Duration of response
3. Overall survival
4. Best Overall Response
5. DCR at 8 weeks assessed by Independent Central Review (1st line part) and by investigators according to RECIST 1.1 (2nd line part)
6. PFS, duration of response, OS, overall response rate (ORR) according to ILDs pattern on CT scan (centralized review) and severity (VC/DLCO).
7. Efficacy (PFS, duration of response, OS and Best Overall Response) and respiratory evolution (number of exacerbations of ILD) with or without anti-fibrosing treatment.
8. Overall health status assessed using the FACT-L questionnaire
9. Incidence, nature, and severity of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 6.0
10. 2nd line: Incidence, nature, and severity of immune related adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v6.0).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Intergroupe Francophone De Cancerologie Thoracique

Sponsor organisation

Intergroupe Francophone De Cancerologie Thoracique

Address

10 Rue De La Grange Bateliere

City

Paris

Postcode

75009

Country

France

Scientific contact point

Organisation

Intergroupe Francophone De Cancerologie Thoracique

Contact name

Contact

Public contact point

Organisation

Intergroupe Francophone De Cancerologie Thoracique

Contact name

Contact

Third parties 1

Locations

1 EU/EEA country · 31 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications