Patients With ES-SCLC and ECOG PS=2 Receiving Atezolizumab-Carboplatin-Etoposide

NCT04221529 | Completed Phase 2 DMC

• 1 other identifier: AIO-TRK-0119
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 19

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.

Conditions

SCLC, Extensive Stage

Keywords

Atezolizumab

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  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.

  Measured from first dose of experimental IMP (or first dose of chemotherapy, whichever occurs first) through study completion, an average of one year.

Secondary Outcomes (5)

• 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.

• 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.

• Quality of life (EORTC-QLQ-C30)

  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.

Study Arms (1)

Atezolizumab

EXPERIMENTAL

Four 21-day cycles of induction therapy with atezolizumab+carboplatin+etoposide followed by 21-day cycles of maintenance therapy with atezolizumab.

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

1200 mg i.v. on day 1 of each cycle

Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ECOG 2
• 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 \[Subjects under therapeutic anticoagulation are permitted.\]
• bilirubin \< 1.5 x ULN
• AST (SGOT)/ALT (SGPT) \< 3 x institutional ULN (\< 5 x ULN in case of liver metastases)
• creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 45 mL/min
• Availability of tumor tissue/block

You may not qualify if:

• 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).
• 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
• history of allogeneic tissue/solid organ transplant
• diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of IMP
• other active malignancy requiring treatment
• clinically significant or symptomatic cardiovascular/cerebrovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) within 6 months before enrolment
• Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year).
• Known hypersensitivity to carboplatin, etoposide or atezolizumab or any of the constituents of the product.

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Hoffmann-La Roche: collaborator

Study Sites (19)

Klinikum Klagenfurt

Klagenfurt, 9020, Austria

Location

Universitätsklinikum Krems

Krems, 3500, Austria

Location

Karl Landsteiner Institut für Lungenforschung und Pneumologische Onkologie c/o Wilhelminenspital der Stadt Wien

Vienna, 1160, Austria

Location

St. Josef Hospital

Bochum, 44791, Germany

Location

Klinikum Esslingen GmbH

Esslingen am Neckar, 73730, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Niels-Stensen-Kliniken

Georgsmarienhütte, 49124, Germany

Location

LungenClinic Grosshansdorf GmbH

Großhansdorf, 22927, Germany

Location

Krankenhaus Martha-Maria Halle-Dölau

Halle, 06120, Germany

Location

Asklepios Klinik Altona

Hamburg, 22763, Germany

Location

Universität Heidelberg

Heidelberg, 69126, Germany

Location

Klinikum Löwenstein gGmbH

Löwenstein, 74245, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH

Marburg, 35043, Germany

Location

Johannes Wesling Klinikum

Minden, 32429, Germany

Location

Klinikum der Universität München

München, 80336, Germany

Location

Brüderkrankenhaus St. Josef

Paderborn, 33098, Germany

Location

Fachkliniken Wangen

Wangen, 88239, Germany

Location

Helios Dr. Horst Schmidt Kliniken Wiesbaden

Wiesbaden, 65199, Germany

Location

Helios Universitätsklinikum

Wuppertal, 42283, Germany

Location

Related Links

• AIO - Working Group for Medical Oncology from the German Cancer Society
• AIO-Studien-gGmbH

MeSH Terms

Interventions

atezolizumab

Study Officials

• Martin Reck, Prof. Dr.

  LungenClinic Grosshansdorf

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2019
• First Posted: January 9, 2020
• Study Start: January 6, 2020
• Primary Completion: April 12, 2024
• Study Completion: April 11, 2025
• Last Updated: September 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (16); AU (3)