A Multicenter Randomized Open Label Phase II Study Evaluating the Efficacy and the Tolerance of Adding Cemiplimab to Sequential hyPOfractionated chemoRADiotherapy in Unfit or Elderly Patients With Unresectable Stage III Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 152
- 试验地点
- 25
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Patients must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
- •Age ≥ 18 years.
- •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
- •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
- •Patients eligible for treatment with sequential radio-chemotherapy validated by multidisciplinary committee.
- •Measurable disease according to RECIST 1.1 per investigator assessment. The radiological assessment has to be done within the timelines indicated.
- •Respiratory function:
- •FEV1 ≥ 40% of theoretical value,
- •DLCO ≥ 40%.
- •Bone marrow function:
- •absolute neutrophil count (ANC) ≥ 1.5.109/L,
- •platelets ≥ 100.109/L,
- •hemoglobin ≥ 9 g/dl.
- •Renal and hepatic function:
- •estimated creatinine clearance ≥ 45 ml/min,
- •bilirubin ≤1.5xULN,
- •AST ALT ≤3xULN,
- •Albumin ≥28g/dl.
- •Participant has national health insurance coverage.
- •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.
- •Expression of PD-L1 as assessed locally by the investigator center.
排除标准
- •Immunotherapy or chemotherapy contra-indicated.
- •Patients eligible for treatment with concomitant radio-chemotherapy validated by multidisciplinary committee.
- •Stage I or II NSCLC.
- •Previously received a treatment with anti-PD1/PDL1, anti-CTLA, or other antineoplastic immunotherapy or chemotherapy for NSCLC.
- •Histology other than primary non-small cell lung cancer.
- •Known activating EGFR mutation or ALK or ROS1 translocation.
- •Metastatic NSCLC including brain metastasis.
- •Patients not eligible for curative radiotherapy (tumor extension, predictable dose constraints that cannot be met).
- •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.
- •Weight loss ≥15% of total body weight in the last 6 months.
- •ECOG PS upper 2
- •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.
- •History of idiopathic pulmonary fibrosis, organized pneumopathy or signs of active interstitial pulmonary pathology on CT scan.
- •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.
- •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.
- •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.
- •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).
- •History of thoracic radiotherapy.
- •Live attenuated vaccine received within 28 days of starting chemotherapy
- •History of organ or bone marrow transplantation.
- •Major surgery within 4 weeks of starting treatment.
- •Patient already included in another therapeutic trial.
- •Positive pregnancy test or breastfeeding woman.
- •Protected adults (under guardianship or curatorship).
- •Inability to undergo medical monitoring of the study (for geographical, social and/or physical reasons).
- •Patients unable to understand the study.
研究组 & 干预措施
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.
干预措施: Curative hypofractionated radiotherapy (Radiation)
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.
干预措施: Carboplatin (Drug)
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.
干预措施: Curative hypofractionated radiotherapy (Radiation)
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.
干预措施: Cemiplimab (Drug)
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.
干预措施: Paclitaxel (Drug)
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.
干预措施: Cemiplimab (maintenance) (Drug)
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.
干预措施: Carboplatin (Drug)
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.
干预措施: Cemiplimab (maintenance) (Drug)
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.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: About 18 months
Time from randomization to progression or death.
次要结局
- OS at 12 months(At 12 months)
- Objective Response Rate (ORR)(About 18 months)
- PFS at 12 months(At 12 months)
- PFS at 18 months(At 18 months)
- OS at 3 year(At 3 year)
- Acute and late grade 3-4 toxicity rates of consolidation immunotherapy(Up to 90 days after the end of immunotherapy)
- Disease Control Rate (DCR)(About 18 months)
- PFS at 3 year(At 3 year)
- Overall Survival (OS) curve(About 3 year)
- OS at 18 months(At 18 months)
- Acute and late grade 3-4 toxicity rates of neoadjuvant chemoimmunotherapy before hypofractionated radiotherapy(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)
- 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)