A Study of Atezolizumab With or Without Tiragolumab Consolidation in Limited Stage Small Cell Lung Cancer

Carcinoma, Small Cell Lung Clinical Trial

Official title:

A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 2 Study to Investigate the Efficacy and Safety of Atezolizumab With or Without Tiragolumab as Consolidation Therapy in Patients With Limited Stage Small Cell Lung Cancer Who Have Not Progressed After Chemoradiotherapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04308785
• Other study ID #: ML41257
• Status: Terminated
• Phase: Phase 2
• Start date: December 1, 2021
• Est. completion date: July 25, 2023

Study information

• Verified date: October 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, double-blind, placebo-controlled, randomized, phase II study to investigate the efficacy and safety of Atezolizumab with or without Tiragolumab as consolidation therapy in participants with limited stage small cell lung cancer who have not progressed during/after chemoradiotherapy.

Description:

Participants can receive concurrent or sequential chemoradiotherapy (CRT) as per local standard of care, but they must be randomized within 6 weeks from completion of chemoradiotherapy. Participants should receive 4 cycles of chemotherapy and radiotherapy dose of 56-64 Gy (once daily) before randomization, and those participants who have not progressed during/after CRT will be stratified by response to CRT, radiotherapy timing, and be randomized in a 1:1 ratio to Atezolizumab+Tiragolumab arm or Atezolizumab+placebo arm.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: July 25, 2023
• Est. primary completion date: July 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed Informed Consent Form
• ECOG performance status of 0 or 1
• Histologically confirmed limited-stage SCLC.
• Patients who have not progressed during/after chemoradiotherapy.
• Concurrent or sequential chemoradiotherapy per local clinical practice must have been completed within 6 weeks prior to the first study treatment. If concurrent CRT is used, at least two cycles of chemotherapy should have been conducted during radiotherapy. If sequential radiotherapy is used, induction chemotherapy should be given 2 cycles of chemotherapy before thoracic radiotherapy.
• Adequate hematologic and end organ function.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the final dose of atezolizumab or placebo, and 90 days after the final dose of tiragolumab or placebo, and 6 months for chemotherapy after the last dose of chemotherapy treatment, whichever is later.
• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm.
• Patients must have recovered from all acute toxicities from previous therapy, excluding alopecia and toxicities related to prior therapy.
• Patients must submit a pre-treatment tumor tissue sample.

Exclusion Criteria:

• Histology mixtured or Extensive-stage SCLC (per the Veterans Administration Lung Study Group (VALG) staging system).
• Uncontrolled pleural effusion or pericardial effusion requiring recurrent drainage procedures
• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, including significant liver disease
• Malignancies other than SCLC within 5 years prior to study treatment initiation, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab and 90 days after the final dose of tiragolumab, and 6 months for chemotherapy after the final dose of the chemotherapy treatment.
• Active or history of autoimmune disease or immune deficiency
• Uncontrolled or symptomatic hypercalcemia
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• Positive test result for HIV
• Patients with active hepatitis B or hepatitis C virus
• Active tuberculosis
• Severe infections within 4 weeks prior to study treatment initiation, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Significant cardiovascular disease
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-CTLA4, anti-tigit, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Unresolved toxic effects of grade 2 or higher (CTCAE 5.0), including grade = 2 pneumonitis from previous therapy
• Active EBV infection or known or suspected chronic active EBV infection at screening.

Related Conditions & MeSH terms

• Carcinoma, Small Cell
• Carcinoma, Small Cell Lung
• Small Cell Lung Carcinoma

Intervention

Drug:
• Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg intravenously on the first day of each 21-day cycle.
• Tiragolumab
Tiragolumab will be administered at a dose of 600 mg intravenously on the first day of each 21-day cycle.

Other:
• Placebo
Placebo matching to tiragolumab will be administered at a dose of 600 mg intravenously on the first day of each cycle.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing
China	Jilin Cancer Hospital	Changchun
China	Hu Nan Provincial Cancer Hospital	Changsha
China	Sichuan Cancer Hospital	Chengdu City
China	Southwest Hospital , Third Military Medical University	Chongqing
China	Fujian Cancer Hospital	Fuzhou
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou
China	Sun Yet-sen University Cancer Center	Guangzhou City
China	Harbin Medical University Cancer Hospital	Harbin
China	Anhui Province Cancer Hospital	Hefei City
China	Shandong Cancer Hospital	Jinan
China	Guangxi Cancer Hospital of Guangxi Medical University	Nanning
China	Fudan University Shanghai Cancer Center; Medical Oncology	Shanghai City
China	Tianjin Cancer Hospital	Tianjin
China	Tumor Center,Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan
China	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an
China	Henan Cancer Hospital	Zhengzhou

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigator Assessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population	PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be calculated based on disease status evaluated by the investigator according to RECIST v1.1.	Randomization up to approximately 48 months
Secondary	Overall Survival (OS) in the ITT Population	OS is defined as the time from randomization to death from any cause or last follow-up.	Randomization up to approximately 48 months
Secondary	PFS Rate at 1 Year and 2 Years in the ITT Ppulation	PFS rate at 1 year and 2 years, defined as the proportion of patients remaining stable disease or ongoing response per RECIST v1.1 at 1 year and 2 years from the time of randomization.	Baseline to 1 Year and 2 Years
Secondary	OS Rate at 1 Year, 2 Years and 3 Years in the ITT Population	OS rate at 1 year, 2 years and 3 years is defined as the proportion of patients remaining alive 1 year, 2 years and 3 years from the time of randomization.	Baseline to 1 Year, 2 Years and 3 Years
Secondary	Objective Response Rate (ORR) in the ITT Population	ORR is defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.1 in patients who have measurable disease at baseline.	Randomization up to approximately 48 months
Secondary	Duration of Response (DOR) in the ITT Population	DOR is defined as the time interval from first occurrence of a documented objective response to the time of disease progression as determined by the investigator according to the RECIST v1.1 or death from any cause, whichever occurs first, in the patients who have experienced a CR or PR (unconfirmed) during the study.	Time from first documentation of complete response (CR) or partial response (PR) up to approximately 48 months
Secondary	Investigator Accessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population by Response to Chemoradiotherapy (CRT) [Stable Disease (SD) vs. Complete Response (CR)/Partial Response (PR)]	PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be calculated based on disease status evaluated by the investigator according to RECIST v1.1.	Randomization up to approximately 33 months
Secondary	Overall Survival (OS) in the ITT Population by Response to CRT (SD vs. CR/PR)	OS is defined as the time from randomization to death from any cause or last follow-up.	Randomization up to approximately 48 months
Secondary	Objective Response Rate (ORR) in the ITT Population by Response to CRT (SD vs. CR/PR)	ORR is defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.1.	Randomization up to approximately 48 months
Secondary	Investigator Accessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population by Radiotherapy Timing (Concurrent vs. Sequential)	PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be calculated based on disease status evaluated by the investigator according to RECIST v1.1.	Randomization up to approximately 48 months
Secondary	Overall Survival (OS) in the ITT Population by Radiotherapy Timing (Concurrent vs. Sequential)	OS is defined as the time from randomization to death from any cause or last follow-up.	Randomization up to approximately 48 months
Secondary	Objective Response Rate (ORR) in the ITT Population by Radiotherapy Timing (Concurrent vs. Sequential)	ORR is defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.1.	Randomization up to approximately 48 months
Secondary	Percentage of Participants With All Adverse Events Related to Atezolizumab and Atezolizumab + Tiragolumab Treatment in the ITT Population		Baseline up to approximately 48 months
Secondary	Percentage of Participants With Serious and Non-Serious Immune Mediated Adverse Events Related to Atezolizumab and Atezolizumab + Tiragolumab Treatment in the ITT Population		Baseline up to approximately 48 months
Secondary	Percentage of Participants With All Adverse Events Related to Treatment in the ITT Population		Baseline up to approximately 48 months
Secondary	Time to Deterioration (TTD) in Patient-Rported Lung Cancer Symptoms	TTD is defined as the time from randomization to a patient's first =10-point score change from baseline in a scale maintained for at least two consecutive PRO assessments, or followed by death within 3 weeks of the first =10-point score change.	Randomization up to approximately 48 months
Secondary	EORTC QLQ-C30 Score	EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 Questionnaire, is a validated, reliable self-report measure. It consists of 30 questions that assess five aspects of patient functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health/quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. Scale scores can be obtained for the multi-item scales.	Day 1 of first 3 cycles (each cycle is 21 days) then with tumor assessments & 3 months after radiographic disease progression or for patients who continue atezolizumab after radiographic disease progression loss of clinical benefit up to approx 48 months
Secondary	EORTC QLQ-LC13 Score	The EORTC, European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, QLQ-LC13 is a modular supplement to the EORTC quality-of-life questionnaire for use in lung cancer. This module incorporates one multiple-item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis.	Day 1 of first 3 cycles (cycle length=21 days), then with tumor assessments & 3 months after radiographic disease progression or for patients who continue atezolizumab after radiographic disease progression loss of clinical benefit up to approx 48 months
Secondary	EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index Based and Visual Analogue Scale (VAS) Scores	The EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L), is a validated self-report health status questionnaire that is used to calculate a health status utility score for use in health economic analyses. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a visual analogue scale (VAS) that measures health state. Published weighting systems allow for creation of a single composite score of the patient's health status.	Day 1 of first 3 cycles (each cycle is 21 days) then with tumor assessments & 3 months after radiographic disease progression or for patients who continue atezolizumab after radiographic disease progression loss of clinical benefit up to approx 48 months