Clinical trial NCT06656598: Adjuvant Chemotherapy +/- Cemiplimab and Sequential Hypofractionated Radiotherapy in Unfit or Elderly Patients With Stage III Lung Cancer
Official title: A Multicenter Randomized Open Label Phase II Study Evaluating the Efficacy and the Tolerance of Immunochemotherapy and of Sequential Hypofractionated Radiotherapy in Unfit or Elderly Patients With Unresectable Stage III Non Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Stage III NSCLC
Keywords: NSCLC
NSCLC, Stage III
Unfit or elderly patients
IFCT
Lead sponsor: Intergroupe Francophone de Cancerologie Thoracique
Sponsor class: OTHER
First posted: 2024-10-24
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: About 18 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: About 18 months
measure: Disease Control Rate (DCR)
timeFrame: About 18 months
measure: PFS at 12 months
timeFrame: At 12 months
measure: PFS at 18 months
timeFrame: At 18 months
measure: PFS at 3 year
timeFrame: At 3 year
measure: Overall Survival (OS) curve
timeFrame: About 3 year
measure: OS at 12 months
timeFrame: At 12 months
measure: OS at 18 months
timeFrame: At 18 months
measure: OS at 3 year
timeFrame: At 3 year
measure: Acute and late grade 3-4 toxicity rates of neoadjuvant chemoimmunotherapy before hypofractionated radiotherapy
timeFrame: Up to 90 days after the end of immunotherapy
measure: To evaluate the quality of life of patients receiving neoadjuvant chemoimmunotherapy before hypofractionated radiotherapy with questionnaire EORTC Quality of Life Questionnaire - Core C30 (QLQ-C30)
timeFrame: About 18 months
measure: To evaluate the quality of life of patients receiving neoadjuvant chemoimmunotherapy before hypofractionated radiotherapy with questionnaire EORTC Quality of Life Questionnaire - Lung Cancer LC29 (QLQ-LC29).
timeFrame: About 18 months
Other outcomes:
Locations:
city: Angers
country: France
facility: Angers - Centre Paul Papin
city: Angers
country: France
facility: Angers - CHU
city: Avignon
country: France
facility: Avignon - CH
city: Boulogne
country: France
facility: Boulogne - Ambroise Paré
city: Brest
country: France
facility: Brest - CHU
city: Caen
country: France
facility: Caen - CHU
city: Caen
country: France
facility: Caen - CRLCC
city: Créteil
country: France
facility: Créteil - CHI
city: Dijon
country: France
facility: Dijon - CRLCC
city: Le Mans
country: France
facility: Le Mans - CHG
city: Lille
country: France
facility: Lille - CRLCC
city: Marseille
country: France
facility: Marseille - APHM
city: Mulhouse
country: France
facility: Mulhouse - GHRMSA
city: Paris
country: France
facility: Paris - Bichat
city: Paris
country: France
facility: Paris - Hôpital Cochin
city: Paris
country: France
facility: Paris - Tenon
city: Pessac
country: France
facility: Bordeaux - CHU
city: Pierre-benite
country: France
facility: Lyon - HCL
city: Rennes
country: France
facility: Rennes - CHU
city: Rouen
country: France
facility: Rouen - Centre Henri Becquerel
city: Saint-Herblain
country: France
facility: Nantes - CRLCC
city: Strasbourg
country: France
facility: Strasbourg - CRLCC
city: Toulouse
country: France
facility: Toulouse - CHU
city: Tours
country: France
facility: Tours - CHU
city: Vandoeuvre-les-nancy
country: France
facility: Vandoeuvre-lès-Nancy - CRLCC
city: Vantoux
country: France
facility: Metz - Hôpital Robert Schuman
Study officials:
References: