Adjuvant Chemotherapy +/- Cemiplimab and Sequential Hypofractionated Radiotherapy in Unfit or Elderly Patients With Stage III Lung Cancer

NCT ID: NCT06656598

Last Updated: 2025-04-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

152 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-30

Study Completion Date

2032-01-31

Brief Summary

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The use of neoadjuvant immuno-chemotherapy could improve survival outcomes of patients eligible for sequential radio-chemotherapy comparing to the benefit already obtained with maintenance immunotherapy.

Detailed Description

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Conditions

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Stage III NSCLC

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A (neoadjuvant chemotherapy only)

Patients will receive neoadjuvant chemotherapy alone with carboplatin AUC 5 D1 and paclitaxel 80mg/m² D1 D8 D15 (3 cycles of 4 weeks). Patients will subsequently receive curative hypofractionated radiotherapy (55 Gy/20fr). After radiotherapy, patients will receive maintenance immunotherapy with Cemiplimab 350 mg every 3 weeks for a period of 12 months.

Group Type ACTIVE_COMPARATOR

Carboplatin

Intervention Type DRUG

Neoadjuvant treatment with Carboplatin AUC 5 D1 (3 cycles of 4 weeks).

Paclitaxel

Intervention Type DRUG

Neoadjuvant treatment with Paclitaxel 80mg/m² D1 (3 cycles of 4 weeks).

Curative hypofractionated radiotherapy

Intervention Type RADIATION

Curative hypofractionated radiotherapy (55 Gy/20fr) after the end of neoadjuvant treatment.

Cemiplimab (maintenance)

Intervention Type DRUG

Maintenance immunotherapy with Cemiplimab 350 mg every 3 weeks after the end of radiotherapy (12 months).

Arm B (neoadjuvant chemo-immunotherapy)

Patients will receive neoadjuvant chemotherapy alone with carboplatin AUC 5 D1 and paclitaxel 80mg/m² D1 D8 D15 and cemiplimab 350 mg D1-D21 (3 cycles of 4 weeks). Patients will subsequently receive curative hypofractionated radiotherapy (55 Gy/20fr). After radiotherapy, patients will receive maintenance immunotherapy with Cemiplimab 350 mg every 3 weeks for a period of 12 months.

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

Neoadjuvant treatment with Carboplatin AUC 5 D1 (3 cycles of 4 weeks).

Paclitaxel

Intervention Type DRUG

Neoadjuvant treatment with Paclitaxel 80mg/m² D1 (3 cycles of 4 weeks).

Cemiplimab

Intervention Type DRUG

Neoadjuvant treatment with Cemiplimab (Libtayo®) 350 mg D1-D21 (3 cycles of 4 weeks).

Curative hypofractionated radiotherapy

Intervention Type RADIATION

Curative hypofractionated radiotherapy (55 Gy/20fr) after the end of neoadjuvant treatment.

Cemiplimab (maintenance)

Intervention Type DRUG

Maintenance immunotherapy with Cemiplimab 350 mg every 3 weeks after the end of radiotherapy (12 months).

Interventions

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Carboplatin

Neoadjuvant treatment with Carboplatin AUC 5 D1 (3 cycles of 4 weeks).

Intervention Type DRUG

Paclitaxel

Neoadjuvant treatment with Paclitaxel 80mg/m² D1 (3 cycles of 4 weeks).

Intervention Type DRUG

Cemiplimab

Neoadjuvant treatment with Cemiplimab (Libtayo®) 350 mg D1-D21 (3 cycles of 4 weeks).

Intervention Type DRUG

Curative hypofractionated radiotherapy

Curative hypofractionated radiotherapy (55 Gy/20fr) after the end of neoadjuvant treatment.

Intervention Type RADIATION

Cemiplimab (maintenance)

Maintenance immunotherapy with Cemiplimab 350 mg every 3 weeks after the end of radiotherapy (12 months).

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patients must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
2. Patients must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
3. Age ≥ 18 years.
4. Histologically or cytologically confirmed locally advanced non small cell lung cancer (NSCLC) stage IIIA non resectable, IIIB or IIIC accordingly to 8th classification TNM, UICC 2015.
5. Patients over 70 years of age with Eastern Cooperative Oncology Group Performance Status (ECOG PS) PS of 0 to 1.

Or Patients under 70 years of age with ECOG PS of 0 to 1 and a score ≥ 3 according to the Charlson comorbidity criterion or ECOG PS 2.
6. Patients eligible for treatment with sequential radio-chemotherapy validated by multidisciplinary committee.
7. Measurable disease according to RECIST 1.1.
8. Respiratory function:

* FEV1 ≥ 40% of theoretical value,
* DLCO ≥ 40%.
9. Bone marrow function:

* absolute neutrophil count (ANC) ≥ 1.5.109/L,
* platelets ≥ 100.109/L,
* hemoglobin ≥ 9 g/dl.
10. Renal and hepatic function:

* estimated creatinine clearance ≥ 45 ml/min,
* bilirubin ≤1.5xULN,
* AST ALT ≤3xULN,
* Albumin ≥28g/dl.
11. Participant has national health insurance coverage.
12. Effective method of contraception during the treatment and during the 6 months following the last dose for patients of childbearing potential and for male subjects who are sexually active with a woman of childbearing potential.

Exclusion Criteria

1. Immunotherapy or chemotherapy contra-indicated.
2. Patients eligible for treatment with concomitant radio-chemotherapy validated by multidisciplinary committee.
3. Stage I or II NSCLC.
4. Previously received a treatment with anti-PD1/PDL1, anti-CTLA, or other antineoplastic immunotherapy or chemotherapy for NSCLC.
5. Histology other than primary non-small cell lung cancer.
6. Patients with an activating EGFR mutation or ALK or ROS1 translocation.
7. Metastatic NSCLC including brain metastasis.
8. Patients not eligible for curative radiotherapy (tumor extension, predictable dose constraints that cannot be met).
9. Severe uncontrolled comorbidities or severe intercurrent disease: acute coronary syndrome less than 3 months old, unstable angina, heart failure with LVEF ≤30%, uncontrolled hypertension, Child B or C cirrhosis, severe sepsis, myocarditis or any other active conditions that would contraindicate chemotherapy, immunotherapy, or radiotherapy in the opinion of the investigator.
10. Weight loss ≥15% of total body weight in the last 6 months.
11. ECOG PS upper 2
12. Active autoimmune pathology. History of autoimmune pathology including myasthenia, Guillain-Barre syndrome, lupus erythematosus, antiphospholipid syndrome, Wegener's granulomatosis, glomerulonephritis, inflammatory bowel disease, vasculitis, sarcoidosis, uveitis. Autoimmune thyroid pathologies under replacement therapy as well as type 1 diabetes under insulin are authorized.
13. History of idiopathic pulmonary fibrosis, organized pneumopathy or signs of active interstitial pulmonary pathology on CT scan.
14. Any immunosuppressive therapy received within 28 days and corticosteroids \> 10mg/day of prednisone or equivalent received within 7 days prior the start of chemotherapy excepted hydrocortisone replacement for adrenal insufficiency or pituitary disease not considered immunosuppressive therapy.
15. Chronic active infection including tuberculosis, HIV, hepatitis B (HBsAg positive) or C. Patients with a history of cured hepatitis B (anti HBc and absence of negative HBs antigen) are eligible. In case of hepatitis C (anti HCV Ac) patients are eligible if the HCV PCR is negative.
16. Severe infections (including covid-19 infection) within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
17. History of neoplastic disease less than 3 years old or progressive (except basal cell carcinoma of the skin and carcinoma in situ of the uterus).
18. History of thoracic radiotherapy.
19. Live attenuated vaccine received within 28 days of starting chemotherapy
20. History of organ or bone marrow transplantation.
21. Major surgery within 4 weeks of starting treatment.
22. Patient already included in another therapeutic trial.
23. Positive pregnancy test or breastfeeding woman.
24. Protected adults (under guardianship or curatorship).
25. Inability to undergo medical monitoring of the study (for geographical, social and/or physical reasons).
26. Patients unable to understand the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Intergroupe Francophone de Cancerologie Thoracique

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Angers - Centre Paul Papin

Angers, , France

Site Status

Angers - CHU

Angers, , France

Site Status

Avignon - CH

Avignon, , France

Site Status

Boulogne - Ambroise Paré

Boulogne, , France

Site Status

Brest - CHU

Brest, , France

Site Status

Caen - CHU

Caen, , France

Site Status

Caen - CRLCC

Caen, , France

Site Status

Créteil - CHI

Créteil, , France

Site Status

Dijon - CRLCC

Dijon, , France

Site Status

Le Mans - CHG

Le Mans, , France

Site Status

Lille - CRLCC

Lille, , France

Site Status

Marseille - APHM

Marseille, , France

Site Status

Mulhouse - GHRMSA

Mulhouse, , France

Site Status

Paris - Bichat

Paris, , France

Site Status

Paris - Hôpital Cochin

Paris, , France

Site Status

Paris - Tenon

Paris, , France

Site Status

Bordeaux - CHU

Pessac, , France

Site Status

Lyon - HCL

Pierre-Bénite, , France

Site Status

Rennes - CHU

Rennes, , France

Site Status

Rouen - Centre Henri Becquerel

Rouen, , France

Site Status

Nantes - CRLCC

Saint-Herblain, , France

Site Status

Strasbourg - CRLCC

Strasbourg, , France

Site Status

Toulouse - CHU

Toulouse, , France

Site Status

Tours - CHU

Tours, , France

Site Status

Vandoeuvre-lès-Nancy - CRLCC

Vandœuvre-lès-Nancy, , France

Site Status

Metz - Hôpital Robert Schuman

Vantoux, , France

Site Status

Countries

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France

Central Contacts

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Contact IFCT

Role: CONTACT

+33 1.56.81.10.45

Facility Contacts

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Frédéric BIGOT, Dr

Role: primary

+33 1.56.81.10.45

Youssef OULKHOUIR, Dr

Role: primary

+33 1.56.81.10.45

Nicolas POUREL, Dr

Role: primary

+33 1.56.81.10.45

Etienne GIROUX LEPRIEUR, Pr

Role: primary

+33 1.56.81.10.45

François LUCIA, Dr

Role: primary

+33 1.56.81.10.45

Jeannick MADELAINE, Dr

Role: primary

+33 1.56.81.10.45

Hubert CURCIO, Dr

Role: primary

+33 1.56.81.10.45

Jean Bernard AULIAC, Pr

Role: primary

+33 1.56.81.10.45

Etienne MARTIN, Dr

Role: primary

+33 1.56.81.10.45

Olivier MOLINIER, Dr

Role: primary

33 1.56.81.10.45

Florence LE TINIER, Dr

Role: primary

+33 1.56.81.10.45

Laurent GREILLIER, Pr

Role: primary

+33 1.56.81.10.45

Didier DEBIEUVRE, Dr

Role: primary

+33 1.56.81.10.45

Valérie GOUNANT, Pr

Role: primary

+33 1.56.81.10.45

Marie WISLEZ, Pr

Role: primary

+33 1.56.81.10.45

Eleonor RIVIN DEL CAMPO, Dr

Role: primary

+33 1.56.81.10.45

Claire BARDEL, Dr

Role: primary

+33 1.56.81.10.45

Sébastien COURAUD, Pr

Role: primary

+33 1.56.81.10.45

Charles RICORDEL, Dr

Role: primary

+33 1.56.81.10.45

Sébastien THUREAU, Pr

Role: primary

+33 1.56.81.10.45

Judith RAIMBOURG, Dr

Role: primary

+33 1.56.81.10.45

Delphine ANTONI, Dr

Role: primary

+33 1.56.81.10.45

Julien MAZIERES, Pr

Role: primary

+33 1.56.81.10.45

Delphine CARMIER, Dr

Role: primary

+331.56.81.10.45

Jean-Christophe FAIVRE, Dr

Role: primary

+33 1.56.81.10.45

Benoît GODBERT, Dr

Role: primary

+33 1.56.81.10.45

Other Identifiers

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IFCT-2401

Identifier Type: -

Identifier Source: org_study_id

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