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

April 22, 2026 updated by: Intergroupe Francophone de Cancerologie Thoracique

Phase II Trial Assessing 1st Line and 2nd Line Treatment in Patients With Advanced Non-Small Cell Lung Carcinoma and Interstitial Lung Disease

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

108

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Contact IFCT
  • Phone Number: +33 1 56 81 10 45
  • Email: contact@ifct.fr

Study Locations

  • France
      • Angers, France
      • Besançon, France
      • Bobigny, France
        • Bobigny - APHP - Hôpital Avicenne
        • Contact:
      • Boulogne-Billancourt, France
        • Boulogne - APHP Ambroise Paré
        • Contact:
          • Pr Etienne GIROUX LEPRIEUR
          • Phone Number: +33 156811046
          • Email: contact@ifct.fr
      • Boulogne-sur-Mer, France
        • Boulogne-Sur-Mer - CH
        • Contact:
      • Brest, France
        • Brest - CHU
        • Contact:
          • Margaux GEIER, Dr
      • Caen, France, 14000
        • Caen - CHU Côte de Nacre
        • Contact:
          • Jeannick MADELAINE, Dr
      • Clermont-Ferrand, France
        • Clermont-Ferrand - CHU
        • Contact:
      • Colmar, France, 68000
        • Colmar - CH
        • Contact:
          • Lionel MOREAU, Dr
      • Créteil, France
        • Créteil - CHI
        • Contact:
      • Dijon, France
        • Dijon - CHU Bocage
        • Contact:
      • Grenoble, France, 38000
        • Grenoble - CHU
        • Contact:
          • Anne-Claire TOFFART, Dr
      • Lille, France
        • Lille - CHU
        • Contact:
      • Lyon, France
        • Lyon - HCL
        • Contact:
      • Marseille, France
        • Marseille - AP-HM Hôpital Nord
        • Contact:
      • Marseille, France
        • Marseille - Institut Paoli Calmette
        • Contact:
      • Metz, France
        • Metz - Hôpital Robert Schuman
        • Contact:
      • Montpellier, France
        • Montpellier - CHU
        • Contact:
      • Nantes, France
        • Nantes - CHU Hôpital Laënnec
        • Contact:
      • Paris, France
      • Paris, France
      • Paris, France
        • Paris - APHP Cochin
        • Contact:
      • Paris, France, 75020
      • Paris, France
        • Paris - APHP Pitié-salpêtrière
        • Contact:
      • Pessac, France
        • Bordeaux - CHU
        • Contact:
      • Pringy, France
        • Annecy - CH
        • Contact:
          • Valérie PAULUS-JACQUEMET
          • Phone Number: +33 1.56.81.10.45
          • Email: contact@ifct.fr
      • Rennes, France
        • Rennes - CHU
        • Contact:
          • Charles RICORDEL, Dr
          • Phone Number: +33 1.56.81.10.45
          • Email: contact@ifct.fr
      • Strasbourg, France, 63000
        • Strasbourg - NHC
        • Contact:
          • Céline MASCAUX, Dr
          • Phone Number: +33 1.56.81.10.45
          • Email: contact@ifct.fr
      • Suresnes, France
        • Suresnes - Foch
        • Contact:
      • Tours, France
      • Villefranche-sur-Saône, France
        • Villefranche-Sur-Saône - Hôpital Nord-Ouest
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria for both parts:

  • 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.
  • Stage IIIB or IIIC non-eligible to radiation therapy or IV (8th TNM classification, UICC 2015). For other less advanced stages but rejected for any local treatment, possible inclusion discussion with the sponsor.
  • 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.

Inclusion Criteria for first-line part:

  • 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.
  • ILD criteria: any type of ILD and any level of severity are allowed Inclusion criteria specific to second-line part
  • 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.
  • 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.
  • 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 for both parts

  • Small cell lung cancer or tumor with mixed histology including a small cell component.
  • Known EGFR activating mutation or ALK or ROS rearrangements. Inclusion of patients with any other oncogene addiction (excluding KRAS mutations) should be discussed with the sponsor on a case-by-case level.
  • 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).
  • Acute exacerbation of interstitial lung disease less than 6 months ago. Exclusion criteria specific to first line part
  • 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.

Exclusion criteria specific to second line part

  • 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.
  • Diagnosis of interstitial lung disease with manifestations of autoimmunity (IPAF) according to ATS/ERS criteria39 Inclusion may be considered on a case-by-case basis following discussion with the sponsor.
  • 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.
  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: First line part (monoarm)
Carboplatine + paclitaxel + bevacizumab for up to 4 cycles
Drug: Paclitaxel
Paclitaxel 90 mg/m² D1, D8, D15 Q4W
Drug: Bevacizumab
Bevacizumab 10 mg/kg D1, D15 Q4W
Drug: Carboplatin
Carboplatin AUC D1 Q4W
Active Comparator: 2nd line part - Arm A
Paclitaxel with or without bevacizumab or pemetred or vinorelbine (gemcitabine is possible but not recommended)
Drug: Paclitaxel
Paclitaxel 90 mg/m² D1, D8, D15 Q4W
Drug: Bevacizumab
Bevacizumab 10 mg/kg D1, D15 Q4W
Drug: Pemetrexed
Pemetrexed 500 mg/m² D1 Q3W
Drug: Vinorelbine
Vinorelbine 25 mg/m² D1, D8 Q3W
Drug: Gemcitabine
Gemcitabine 1150 mg/m² D1, D8 Q3W
Experimental: 2nd line part - Arm B
Nivolumab of pembrolizumab
Drug: Nivolumab
Nivolumab 240 mg D1 Q2W
Drug: Pembrolizumab
Pembrolizumab 200 mg D1 Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
1st line part: disease Control Rate at 8 weeks
Time Frame: 8 weeks from date of inclusion
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
Time Frame: 6 months from randomisation
6 months from randomisation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: About 6 months
About 6 months
Duration of response
Time Frame: About 6 months
About 6 months
Overall Survival
Time Frame: About 20 months
About 20 months
Best overall response
Time Frame: About 6 months
About 6 months
1st line part: Disease control rate at 8 weeks
Time Frame: 8 weeks
Assessed by Independent Central Review
8 weeks
2nd line part: Disease control rate at 8 weeks
Time Frame: 8 weeks
Assessed by Investigators
8 weeks
Progression-free survival according to ILDs pattern on CT scan
Time Frame: About 6 months
About 6 months
Duration of response according to ILDs pattern on CT scan
Time Frame: About 6 months
About 6 months
Overall Survival according to ILDs pattern on CT scan
Time Frame: About 20 months
About 20 months
Best overall response according to ILDs pattern on CT scan
Time Frame: About 6 months
About 6 months
Progression-free survival according to ILDs severity (FVC/DLCO)
Time Frame: About 6 months
About 6 months
Duration of response according to ILDs severity (FVC/DLCO)
Time Frame: About 6 months
About 6 months
Overall Survival according to ILDs severity (FVC/DLCO)
Time Frame: About 20 months
About 20 months
Best overall response according to ILDs severity (FVC/DLCO)
Time Frame: About 6 months
About 6 months
Respiratory evolution (number of exaxerbations of ILD) with or without anti-fibrosing treatment
Time Frame: About 6 months
About 6 months
Progression-free survival with or without anti-fibrosing treatment
Time Frame: About 6 months
About 6 months
Duration of response with or without anti-fibrosing treatment
Time Frame: About 6 months
About 6 months
Overall Survival with or without anti-fibrosing treatment
Time Frame: About 20 months
About 20 months
Best overall response with or without anti-fibrosing treatment
Time Frame: About 6 months
About 6 months
Incidence, nature, and severity of adverse events
Time Frame: About 6 months
Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 6.0
About 6 months
2nd ine part: Incidence, nature, and severity of immune related adverse events
Time Frame: About 6 months
Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 6.0
About 6 months
Overall health status assessed using the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire
Time Frame: About 6 months
About 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Intergroupe Francophone de Cancerologie Thoracique

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 15, 2026

Primary Completion (Estimated)

August 15, 2028

Study Completion (Estimated)

November 15, 2028

Study Registration Dates

First Submitted

February 12, 2026

First Submitted That Met QC Criteria

February 12, 2026

First Posted (Actual)

February 19, 2026

Study Record Updates

Last Update Posted (Actual)

April 27, 2026

Last Update Submitted That Met QC Criteria

April 22, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IFCT-2502 LIMPID
  • 2025-522790-10-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Non Small Cell Lung Cancer Metastatic

Clinical Trials on Paclitaxel

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Germany

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe