Thoracic RadiothErapy with Atezolizumab in Small Cell LUng CanceR Extensive Disease: a Randomized, Open-label, Multicenter Phase II Study

Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest20 sites in 2 countries68 target enrollmentJuly 28, 2020

ConditionsSmall Cell Lung Cancer Extensive Stage Thoracic Radiotherapy

InterventionsAtezolizumab thoracic radiotherapy (TRT)

Overview

Phase: Phase 2
Intervention: Atezolizumab
Conditions: Small Cell Lung Cancer Extensive Stage
Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Enrollment: 68
Locations: 20
Primary Endpoint: Overall survival (OS)
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a multicenter phase 2 clinical trial to investigate the treatment efficacy and feasibility of combining thoracic radiotherapy (TRT) with the IMpower133 regimen in the upfront treatment of ED SCLC patients. Patients with a response after induction therapy with carboplatin/etoposide and atezolizumab will be included into this study to subsequently receive atezolizumab maintenance therapy and will be randomized to receive TRT or not. This trial aims to i.) increase the efficacy of combined atezolizumab- and chemotherapy by adding radiotherapy and ii.) determine the safety and tolerability of the combination of chemotherapeutic, immunological and radiological treatment in the first-line setting of advanced SCLC, and iii.) to collect tumor tissue as well as blood and stool samples for separate biomarker research project.

Registry

clinicaltrials.gov

Start Date

July 28, 2020

End Date

September 2, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Fully-informed written consent and locally required authorization (European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
•Age ≥ 18 years.
•Histologically or cytologically confirmed ED SCLC as defined according to the Veterans Administration Lung Study Group staging system.
•Measurable ED SCLC according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.
•In cases of CR or PR without residual measurable disease after 4 cycles of induction therapy, patients may still be included. In such cases "No Evidence of Disease (NED)" should be reported in eCRF.
•ECOG performance status score of 0 or 1 at screening
•Any response after four cycles of standard chemo-immunotherapy (carboplatin, etoposide, atezolizumab) defined as CR/PR or thoracic SD with CR/PR of extrathoracic lesions as per RECIST 1.1
•Thoracic treatment volume considered treatable using acceptable radiation fields as judged by a radiation oncologist
•28 ± 7 days between last administration of chemo-immunotherapy (carboplatin, etoposide, atezolizumab) and randomization.
•Patients with a history of treated CNS metastases are eligible, if there is no ongoing requirement for corticosteroids as therapy for CNS disease. Before randomization, MRI of brain (with contrast, unless contraindicated) is recommended in subjects with suspected or known brain metastases, as per local standard., Patients with asymptomatic brain metastases that do not require local therapy with irradiation (whole brain irradiation) can be included. In ambiguous cases, consultation with the LKP or his/her delegate is advised.

Exclusion Criteria

•Previous treatment with CD137 agonists, immune-checkpoint blockade therapies, anti-PD-1, or anti-PD-L1 therapeutic antibodies (with the exclusion of prior immunotherapy as defined in inclusion criterion 6).
•Prior therapy for limited-stage SCLC with curative intent.
•Prior radiotherapy of lung and mediastinal lymph nodes within the past 5 years before the first dose of study drug.
•Oxygen-dependent medical condition.
•History or current radiology suggestive of interstitial lung disease (ILD) (including but not limited to idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP)/cryptogenic fibrosing alveolitis (CFA)), non-infectious pneumonitis, drug-induced pneumonitis, idiopathic pneumonitis.
•Criterion removed.
•Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study.
•Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment.
•Any concurrent chemotherapy, investigational product (IMP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replacement therapy) is acceptable.
•Major surgery (as defined by the Investigator) within 4 weeks prior to enrollment into the study; patients must have recovered from effects of any major surgery. Note: Local non-major surgery for palliative intent is acceptable.

Arms & Interventions

Arm A: Atezolizumab + thoracic radiotherapy

Atezolizumab at a fixed dose of 1,200 mg as an IV infusion, on day 1, to be repeated every 3 weeks (Q3W) Thoracic radiation therapy (TRT), 30 Gy in 10 fractions

Intervention: Atezolizumab

Arm A: Atezolizumab + thoracic radiotherapy

Atezolizumab at a fixed dose of 1,200 mg as an IV infusion, on day 1, to be repeated every 3 weeks (Q3W) Thoracic radiation therapy (TRT), 30 Gy in 10 fractions

Intervention: thoracic radiotherapy (TRT)

Arm B: Atezolizumab

Atezolizumab at a fixed dose of 1,200 mg as an IV infusion, on day 1, to be repeated every 3 weeks (Q3W)

Intervention: Atezolizumab

Outcomes

Primary Outcomes

Overall survival (OS)

Time Frame: at 24 month after lat patient randomized

time from randomization to death

Secondary Outcomes

1-year Overall Survival (OS) rate(at 1 year after randomization)
2-year Overall Survival (OS) rate(at 2 years after randomization)
Progression-free survival (PFS)(at study end (approx. 2 years after last patient randomized))
objective response rate (ORR)(at study end (approx. 2 years after last patient randomized))
Frequency of abnormal laboratory parameters(at study end (approx. 2 years after last patient randomized))
frequency of treatment withdrawal(at study end (approx. 2 years after last patient randomized))
completion of radiotherapy(at study end (approx. 2 years after last patient randomized))
Intrathoracic tumor control(at study end (approx. 2 years after last patient randomized))
Incidence, nature, causal relationship and severity of Adverse Events(at study end (approx. 2 years after last patient randomized))
Cancer related quality of life (Functional Assessment of Cancer Therapy for patients with Lung cancer (FACT-L))(at study end (approx. 2 years after last patient randomized))