A Randomized Non-comparative Phase II Study of Anti-PDL1 ATEZOLIZUMAB (MPDL3280A) or Chemotherapy as Second-line Therapy in Patients With Small Cell Lung Cancer (SCLC)
Overview
- Phase
- Phase 2
- Intervention
- Topotecan
- Conditions
- Small Cell Lung Cancer
- Sponsor
- Intergroupe Francophone de Cancerologie Thoracique
- Enrollment
- 73
- Locations
- 18
- Primary Endpoint
- Response Rate in the experimental arm
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
Chemotherapy still constitutes the backbone of small-cell lung cancer (SCLC) therapy, particularly in the extensive disease (ED) stage (ED-SCLC). Despite the fact that a substantial complete response rate could be achieved in SCLC patients receiving etoposide - cisplatin doublet, cure remains the exception. Overall survival in patients receiving this combination is 10 months and progression free survival 6.3 months. At time of progression two options are hitherto accepted: reinduction of carboplatin - etoposide doublet or, for patients unfit for reinduction, topotecan single-drug regimen. However, in both clinical cases, median survival hardly achieves 33 weeks. Consistent data using anti - PDL1 (Programmed death-ligand 1) or anti PD1 (programmed cell death 1) antibodies suggest that they are active as single drug regimens in many malignant diseases. Taking into account the rich tumor infiltrating lymphocyte in pathological specimens of SCLC, we can hypothesize that experimental use of ATEZOLIZUMAB (MPDL3280A) in patients is ethical pending that it demonstrates activity in the second line setting.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed small-cell lung cancer.
- •Extensive or limited disease according to the criteria of the Veteran's Administration Lung Cancer Group: (disease extended is defined as a disease beyond hemi thorax and supraclavicular lymph node areas. Tumor pleural effusion will be considered as extended disease).
- •Targetable tumor lesions according to RECIST 1.
- •Tumor involvement encompassed into a radiotherapy field is eligible as target pending that progression is documented.
- •Tumor sample sent to IFCT for PD-L1 immunohistochemistry
- •Previous platinum - etoposide treatment for at least 2 cycles.
- •Demonstrated progression of the disease other than brain metastasis or carcinomatous meningitis.
- •For the patient relapsing more than one year after the end of the previous treatment, a new histological confirmation is required before randomization.
- •Age over 18 years.
- •Weight loss ≤ 10% during the last three months.
Exclusion Criteria
- •Non-small cell lung cancer or mixed small-cell lung cancer - non small cell cancer.
- •Prior immunotherapy
- •Last dose of the previous treatment received less than 21 days before randomization (washout period).
- •Corticosteroid with a daily dose over 10 mg prednisolone or equivalent for more than 10 days during the previous month.
- •Unstable angina or uncontrolled cardiac disease.
- •Progressive infection (suggested by a fever associated with hyperleukocytosis, increase procalcitonin, and increase of C reactive protein without link with a paraneoplastic syndrome).
- •Patient not able to follow the therapeutic program.
- •Natremia \< 125 mmol/L except in case of corrective treatment before the beginning of the therapy.
- •Hypercalcemia despite corrective treatment (corrected calcemia = Ca++ (mmol) + \[(40-alb (g)) x 0.025\].
- •Psychic or mental disease that do not allow the patient to give informed consent.
Arms & Interventions
Arm A : chemotherapy
Patients randomly assigned to the control arm will receive either: * topotecan (oral 2.3 mg/m² or IV 1.5 mg/m² day 1-4 recommended) * or re-induction by carboplatin - etoposide chemotherapy.
Intervention: Topotecan
Arm A : chemotherapy
Patients randomly assigned to the control arm will receive either: * topotecan (oral 2.3 mg/m² or IV 1.5 mg/m² day 1-4 recommended) * or re-induction by carboplatin - etoposide chemotherapy.
Intervention: Carboplatin
Arm A : chemotherapy
Patients randomly assigned to the control arm will receive either: * topotecan (oral 2.3 mg/m² or IV 1.5 mg/m² day 1-4 recommended) * or re-induction by carboplatin - etoposide chemotherapy.
Intervention: Etoposide
Arm B : immune therapy
Patients randomly assigned to the experimental arm will receive Anti PDL1 ATEZOLIZUMAB (MPDL3280A) at a fixed dose of 1200 mg IV every three weeks until progression or unacceptable toxicity.
Intervention: Atezolizumab
Outcomes
Primary Outcomes
Response Rate in the experimental arm
Time Frame: 6 weeks
Maximum changed in target lesions from baseline at 6 weeks
Secondary Outcomes
- Overall Survival(approximately 8 months)
- Compliance assessed by the number of cycle received by patient(approximately 36 weeks)
- Safety assessed by the maximum grade will be summarized by frequency and proportion of total patients, by system organ class and NCI-CTC, Version 4.0 categories.(approximately 36 weeks)
- Duration of response(approximately 36 weeks)
- Quality of life assessed by scale(approximately 36 weeks)
- Progression Free Survival(approximately 36 weeks)