Stage III NSCLC
Conditions
Keywords
NSCLC, NSCLC, Stage III, Unfit or elderly patients, IFCT
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.
Interventions
DRUGCarboplatin
Neoadjuvant treatment with Carboplatin AUC 5 D1 (3 cycles of 4 weeks).
DRUGPaclitaxel
Neoadjuvant treatment with Paclitaxel 80mg/m² D1 (3 cycles of 4 weeks).
DRUGCemiplimab
Neoadjuvant treatment with Cemiplimab (Libtayo®) 350 mg D1-D21 (3 cycles of 4 weeks).
RADIATIONCurative hypofractionated radiotherapy
Curative hypofractionated radiotherapy (55 Gy/20fr) after the end of neoadjuvant treatment.
Maintenance immunotherapy with Cemiplimab 350 mg every 3 weeks after the end of radiotherapy (12 months).
Sponsors
Intergroupe Francophone de Cancerologie Thoracique
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. Unfit or elderly patients as defined below: * ≥ 70 years , PS 0 to 1, charlson comorbidity criterion : all score * \< 70 years , PS 0 to 1, charlson comorbidity criterion : score ≥ 3 * \< 70 years , PS , charlson comorbidity criterion : all score 6. Patients eligible for treatment with sequential radio-chemotherapy validated by multidisciplinary committee. 7. Measurable disease according to RECIST 1.1 per investigator assessment. The radiological assessment has to be done within the timelines indicated. 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. 13. Expression of PD-L1 as assessed locally by the investigator center.
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. Known 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 (other than NSCLC) less than 3 years old or progressive (except basal cell carcinoma of the skin and carcinoma in situ of the cervix). 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | About 18 months | Time from randomization to progression or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | About 18 months | Proportion of patients who have achieved a best overall response of complete response (CR) or partial response (PR) |
| Disease Control Rate (DCR) | About 18 months | Proportion of patients who have achieved a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) |
| PFS at 12 months | At 12 months | Time from randomization to progression or death. |
| PFS at 18 months | At 18 months | Time from randomization to progression or death. |
| PFS at 3 year | At 3 year | Time from randomization to progression or death. |
| Overall Survival (OS) curve | About 3 year | Time from date of inclusion to the date of death due to any cause. |
| OS at 12 months | At 12 months | Time from date of inclusion to the date of death due to any cause. |
| OS at 18 months | At 18 months | Time from date of inclusion to the date of death due to any cause. |
| OS at 3 year | At 3 year | Time from date of inclusion to the date of death due to any cause. |
| Acute and late grade 3-4 toxicity rates of neoadjuvant chemoimmunotherapy before hypofractionated radiotherapy | Up to 90 days after the end of immunotherapy | Acute and late grade 3-4 toxicity rates by treatment arm according to CTCAE v5.0 up to 90 days after the end of immunotherapy. |
| 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) | About 18 months | Time to symptom deterioration will be defined as the time from inclusion until the date of first clinically meaningful symptom deterioration (an increase in the score from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the subject withdraws from therapy or receives another anticancer therapy prior to symptom deterioration. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core Questionnaire C30 (EORTC QLQ-C30) is a 30 item instrument meant to assess some of the different aspects that define the quality of life of cancer patients. Scale : Not at all / A little / Quite a bit / Very much |
| 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). | About 18 months | Time to symptom deterioration will be defined as the time from inclusion until the date of first clinically meaningful symptom deterioration (an increase in the score from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the subject withdraws from therapy or receives another anticancer therapy prior to symptom deterioration. The EORTC QLQ-LC29 incorporates 5 multi-item scales to assess symptom or quality of life issues. Scale : Not at all / A little / Quite a bit / Very much |
| Acute and late grade 3-4 toxicity rates of consolidation immunotherapy | Up to 90 days after the end of immunotherapy | Acute and late grade 3-4 toxicity rates by treatment arm according to CTCAE v5.0 up to 90 days after the end of immunotherapy. |
Countries
France
Contacts
CONTACTContact IFCT
Outcome results
None listed