Single-Arm Phase II-Study in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) With Poor Performance Status Receiving Atezolizumab-Carboplatin-Etoposide
Overview
- Phase
- Phase 2
- Intervention
- Atezolizumab
- Conditions
- SCLC, Extensive Stage
- Sponsor
- AIO-Studien-gGmbH
- Enrollment
- 70
- Locations
- 19
- Primary Endpoint
- Overall survival (OS)
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
Small cell lung cancer (SCLC) is a rapidly proliferating, neuroendocrine tumor that accounts for about 15% of all lung cancers. Most patients have metastases at primary diagnosis involving sites like bone, adrenal glands, liver and brain.
Compared with non-small-cell lung cancer (NSCLC) SCLC has a unique natural history with a shorter doubling time, higher growth fraction, earlier development of widespread metastases, and uniform initial response to chemo- or radiotherapy.
The combination of cis- or carboplatin and etoposide is the standard of care in the first-line treatment of stage IV (extensive-disease) SCLC (ED-SCLC). Despite response rates of 50-80%, most patients relapse within six months and the median survival time is less than 10 months. Between 14 and 23% of SCLC patients develop brain metastases.
New cytotoxic agents as well as targeted therapies have not been able to show any improvement of survival in this group of patients.
Early phase trials of PD 1/PD L1-blocking immunotherapeutic agents in patients with recurrent or ED SCLC have shown promising response rates and good tolerability. Immunotherapy may also contribute to the efficacy of systemic treatment by maintaining initial responses to chemotherapy. A double-blind, placebo-controlled phase 3 trial indicates that the addition of atezolizumab to standard chemotherapy significantly improves overall survival and progression-free survival compared with chemotherapy alone in treatment-naïve patients with ED-SCLC who are in good general condition (ECOG 0 or 1). However, about one in three SCLC patients has a poor performance status (ECOG≥2), which is associated with even shorter survival times of under eight months. At present, there is little information regarding the feasibility, safety and efficacy of adding atezolizumab to standard chemotherapy for this considerable fraction of patients.
The investigators expect, that atezolizumab in addition to chemotherapy is feasible in patients with stage IV SCLC and reduced performance status and therefore crucial efficacy data can be acquired in this trial to evaluate a putative Phase III transition in this particular patient population.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent including participation in translational research obtained from the subject prior to performing any protocol-related procedures, including screening evaluations that are not SOC.
- •At least one measurable tumor lesion (according to RECIST1.1)
- •Histologically confirmed small cell lung cancer (SCLC)
- •Stage IV disease (according to UICC8)
- •No active autoimmune disease
- •Adequate organ function defined as:
- •neutrophil count \> 1.5 x 109/L
- •thrombocytes ≥ 100 x 109/L
- •hemoglobin ≥ 9 g/dL
- •INR ≤ 1.4 or aPTT ≤ 40 sec during the last 7 days before therapy \[Subjects under therapeutic anticoagulation are permitted.\]
Exclusion Criteria
- •Any preceding systemic anticancer therapy for stage IV SCLC. \[Up to one full-cycle-dosing of carboplatin+etoposide chemotherapy within the context of SOC is permitted prior to study treatment.\] (Note: Prior treatment for limited stage disease allowed).
- •Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lives of previously used trial medication, whichever is longer
- •Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1), anti-Programmed cell death-ligand 1 (anti-PD-L1), anti-Programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor \[TNFR\] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
- •Previous treatment in the present study (does not include screening failure).
- •Symptomatic CNS metastases. \[Patients with asymptomatic brain metastases may be included.\]
- •Major surgery ≤ 28 days before first dose of study treatment
- •Any uncontrolled systemic disease, condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results, including but not limited to:
- •known active HBV, HCV or HIV infection \[Patients who are HIV-positive are allowed in the trial, so long as they are stable on anti-retroviral therapy, have a CD4 count ≥ 200 cells/μL, and have an undetectable viral load at the time of screening.\]
- •active tuberculosis
- •any other active infection requiring systemic therapy
Arms & Interventions
Atezolizumab
Four 21-day cycles of induction therapy with atezolizumab+carboplatin+etoposide followed by 21-day cycles of maintenance therapy with atezolizumab.
Intervention: Atezolizumab
Outcomes
Primary Outcomes
Overall survival (OS)
Time Frame: Measured from first dose of experimental IMP (or first dose of chemotherapy, whichever occurs first) through study completion, an average of one year.
OS is defined as the length of time from first dose of experimental IMP (or first dose of chemotherapy, whichever occurs first) to the date of death. A subject who has not died will be censored at last known date alive.
Secondary Outcomes
- Quality of life (EORTC-QLQ-C30)(Starting from Screening up to an average of one year.)
- Incidence of Treatment-Emergent adverse events, serious adverse events and laboratory abnormalities leading to treatment discontinuation(Starting from Screening up to an average of one year.)
- Objective response rate (ORR) (RECIST 1.1)(Starting from Screening up to an average of one year.)
- Progression-free suvival (PFS)(Starting from Screening up to an average of one year.)
- Quality of life (PRO-CTCAE)(Starting from Screening up to an average of one year.)