Treatment in Patients With Advanced Non-Small Cell Lung Carcinoma and Interstitial Lung Disease

NCT07420439 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: IFCT-2502 LIMPID2025-522790-10-00
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 31

Brief Summary

Lung cancer is a leading cause of cancer-related death worldwide. Interstitial Lung Diseases are closely associated with lung cancer either as complications or comorbidities to be considered for treatment. Recently, a survey concerning the management of lung cancer in patients with ILDs was conducted by the Interstitial Lung Diseases and Thoracic Oncology Assemblies of the European Respiratory Society. Out of 494 practitioners, mostly pulmonologists, this survey showed that the majority of metastatic patients with pulmonary fibrosis would not be treated (69%), but that 25% and 31% of clinicians would offer chemotherapy or immunotherapy, respectively. The systemic therapy is not clearly codified. There is a risk of worsening of ILDs with most of the treatments used in lung cancer including surgery, radiation therapy or certain systemic therapies. The Japanese Society of Pneumology has recently published proposals for care. However, the Asian population is unique in its incidence of ILDs and the frequency of drug toxicities and these recommendations may not be relevant for other populations. Thus, data are still needed to validate carboplatin and weekly paclitaxel as the best regimen for first-line treatment of NSCLC patients with ILD in a caucasian population. In 2nd line setting, immune checkpoint blocker (ICB) in monotherapy or associated with chemotherapy has become an essential part of the therapeutic arsenal in advanced NSCLC. Several agents have been shown to be superior to docetaxel, following platinum-based chemotherapy failure, and have resulted in several marketing authorizations for PD-1 inhibitors (nivolumab, pembrolizumab) and PD-L1 inhibitors (atezolizumab). The long-term benefits of using ICBs as a second-line therapy are now clear. Survival at 5 years is 10% higher than that obtained with docetaxel alone. The safety profile is well known in particular with a risk of pulmonary toxicity. It should be noted that in most trials, patients with ILDs were not included. Therefore, we do not have trial data from these pivotal trials in patients with concomitant ILD. Two prospective studies are available on the use of nivolumab in the second-line setting in patients with idiopathic ILDs. The first, in an Asian population, included 6 patients. It showed an interesting response rate of 50% without grade III or IV pulmonary toxicity or worsening of at 12 weeks. Following this, the same team proposed a multicenter phase 2 study. Included patients had mild ILDs (VCf \>80%) and were treated with nivolumab in 2nd line. The primary objective was PFS at 6 months. 18 patients were treated. 3 patients developed toxicity leading to discontinuation of nivolumab including 2 patients with grade 2 pneumonitis. PFS at 6 months was 56%, response rate was 39% and disease control achieved for 72% of patients. In a recent prospective study in Asia, atezolizumab was administered to patients with moderate IPF and advanced NSCLC. The study was stopped prematurely due to a high incidence of inflammatory pneumonitis. Thus, data are still needed to assess the safety of ICB in NSCLC patients with ILD in second line setting.

Conditions

Non Small Cell Lung Cancer Metastatic; Interstitial Lung Disease (ILD)

Keywords

NSCLC; ILD; chemotherapy; immunotherapy

Outcome Measures

Primary Outcomes (2)

• 1st line part: disease Control Rate at 8 weeks

  Assessed by investigators according to RECIST 1.1.

  8 weeks from date of inclusion

• 2nd line part: Treatment related respiratory worsening leading to discontinuation of treatment during the first 6 months

  6 months from randomisation

Secondary Outcomes (22)

• Progression-free survival

  About 6 months

• Duration of response

  About 6 months

• Overall Survival

  About 20 months

• Best overall response

  About 6 months

• 1st line part: Disease control rate at 8 weeks

  8 weeks

Study Arms (3)

First line part (monoarm)

EXPERIMENTAL

Carboplatine + paclitaxel + bevacizumab for up to 4 cycles

Drug: Paclitaxel; Drug: Bevacizumab; Drug: Carboplatin

2nd line part - Arm A

ACTIVE COMPARATOR

Paclitaxel with or without bevacizumab or pemetred or vinorelbine (gemcitabine is possible but not recommended)

Drug: Paclitaxel; Drug: Bevacizumab; Drug: Pemetrexed; Drug: Vinorelbine; Drug: Gemcitabine

2nd line part - Arm B

EXPERIMENTAL

Nivolumab of pembrolizumab

Drug: Nivolumab; Drug: Pembrolizumab

Interventions

Paclitaxel DRUG

Paclitaxel 90 mg/m² D1, D8, D15 Q4W

2nd line part - Arm A; First line part (monoarm)

Bevacizumab DRUG

Bevacizumab 10 mg/kg D1, D15 Q4W

2nd line part - Arm A; First line part (monoarm)

Carboplatin DRUG

Carboplatin AUC D1 Q4W

First line part (monoarm)

Pemetrexed DRUG

Pemetrexed 500 mg/m² D1 Q3W

2nd line part - Arm A

Vinorelbine DRUG

Vinorelbine 25 mg/m² D1, D8 Q3W

2nd line part - Arm A

Nivolumab DRUG

Nivolumab 240 mg D1 Q2W

2nd line part - Arm B

Pembrolizumab DRUG

Pembrolizumab 200 mg D1 Q3W

2nd line part - Arm B

Gemcitabine DRUG

Gemcitabine 1150 mg/m² D1, D8 Q3W

2nd line part - Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• NSCLC proven histologically. Cytological evidence is allowed if a cytoblock has been prepared.
• Age ≥ 18 years old.
• Performance status ≤ 2.
• Disease measurable according to RECIST criteria 1.1 per investigator assessment.
• 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 ULN except for patients with liver metastases (\< 5x ULN); total bilirubin ≤ 1.5x ULN except for patients with proven Gilbert's syndrome (≤ 5x ULN) or patients with liver metastases (≤ 3.0 mg/dL).
• Life expectancy of at least 12 weeks.
• 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.
• Patient covered by national health insurance.
• Protected adults may participate in the study if they can make decisions regarding their medical treatment in accordance with the guardianship judgment.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• Small cell lung cancer or tumor with mixed histology including a small cell component.
• 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).
• Previous systemic therapy (including but not limited to chemotherapy, targeted therapy, immunotherapy). 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.
• 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.
• More than one line of treatment.
• Any prior immunotherapy.
• 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.
• Corticosteroid therapy \> 10 mg daily oral prednisone or equivalent.
• Immunosuppressive therapy within two weeks prior to randomization.
• Patients who have had major surgery ≤ 3 weeks before randomization.

Sponsors & Collaborators

• Intergroupe Francophone de Cancerologie Thoracique: lead

Study Sites (31)

Angers - CHU

Angers, France

Location

Besançon - CHU

Besançon, France

Location

Bobigny - APHP - Hôpital Avicenne

Bobigny, France

Location

Boulogne - APHP Ambroise Paré

Boulogne-Billancourt, France

Location

Boulogne-Sur-Mer - CH

Boulogne-sur-Mer, France

Location

Brest - CHU

Brest, France

Location

Caen - CHU Côte de Nacre

Caen, 14000, France

Location

Clermont-Ferrand - CHU

Clermont-Ferrand, France

Location

Colmar - CH

Colmar, 68000, France

Location

Créteil - CHI

Créteil, France

Location

Dijon - CHU Bocage

Dijon, France

Location

Grenoble - CHU

Grenoble, 38000, France

Location

Lille - CHU

Lille, France

Location

Lyon - HCL

Lyon, France

Location

Marseille - AP-HM Hôpital Nord

Marseille, France

Location

Marseille - Institut Paoli Calmette

Marseille, France

Location

Metz - Hôpital Robert Schuman

Metz, France

Location

Montpellier - CHU

Montpellier, France

Location

Nantes - CHU Hôpital Laënnec

Nantes, France

Location

Paris - APHP - Tenon

Paris, 75020, France

Location

Paris - APHP Bichat

Paris, France

Location

Paris - APHP Cochin

Paris, France

Location

Paris - APHP Pitié-salpêtrière

Paris, France

Location

Paris - Saint Joseph

Paris, France

Location

Bordeaux - CHU

Pessac, France

Location

Annecy - CH

Pringy, France

Location

Rennes - CHU

Rennes, France

Location

Strasbourg - NHC

Strasbourg, 63000, France

Location

Suresnes - Foch

Suresnes, France

Location

Tours - CHU

Tours, France

Location

Villefranche-Sur-Saône - Hôpital Nord-Ouest

Villefranche-sur-Saône, France

Location

MeSH Terms

Conditions

Lung Diseases, Interstitial

Interventions

Paclitaxel; Bevacizumab; Carboplatin; Pemetrexed; Vinorelbine; Nivolumab; pembrolizumab; Gemcitabine

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Contact IFCT

CONTACT

+33 1 56 81 10 45; contact@ifct.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2026
• First Posted: February 19, 2026
• Study Start: May 15, 2026
• Primary Completion (Estimated): August 15, 2028
• Study Completion (Estimated): November 15, 2028
• Last Updated: April 27, 2026

Record last verified: 2026-02

Locations

FR (31)