Clinical trial NCT04308785: A Study of Atezolizumab With or Without Tiragolumab Consolidation in Limited Stage Small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Carcinoma, Small Cell Lung
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-03-16
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Investigator Assessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population
timeFrame: Randomization up to approximately 48 months
Secondary outcomes:
measure: Overall Survival (OS) in the ITT Population
timeFrame: Randomization up to approximately 48 months
measure: PFS Rate at 1 Year and 2 Years in the ITT Ppulation
timeFrame: Baseline to 1 Year and 2 Years
measure: OS Rate at 1 Year, 2 Years and 3 Years in the ITT Population
timeFrame: Baseline to 1 Year, 2 Years and 3 Years
measure: Objective Response Rate (ORR) in the ITT Population
timeFrame: Randomization up to approximately 48 months
measure: Duration of Response (DOR) in the ITT Population
timeFrame: Time from first documentation of complete response (CR) or partial response (PR) up to approximately 48 months
measure: 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)]
timeFrame: Randomization up to approximately 33 months
measure: Overall Survival (OS) in the ITT Population by Response to CRT (SD vs. CR/PR)
timeFrame: Randomization up to approximately 48 months
measure: Objective Response Rate (ORR) in the ITT Population by Response to CRT (SD vs. CR/PR)
timeFrame: Randomization up to approximately 48 months
measure: Investigator Accessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population by Radiotherapy Timing (Concurrent vs. Sequential)
timeFrame: Randomization up to approximately 48 months
measure: Overall Survival (OS) in the ITT Population by Radiotherapy Timing (Concurrent vs. Sequential)
timeFrame: Randomization up to approximately 48 months
measure: Objective Response Rate (ORR) in the ITT Population by Radiotherapy Timing (Concurrent vs. Sequential)
timeFrame: Randomization up to approximately 48 months
measure: Percentage of Participants With All Adverse Events Related to Atezolizumab and Atezolizumab + Tiragolumab Treatment in the ITT Population
timeFrame: Baseline up to approximately 48 months
measure: Percentage of Participants With Serious and Non-Serious Immune Mediated Adverse Events Related to Atezolizumab and Atezolizumab + Tiragolumab Treatment in the ITT Population
timeFrame: Baseline up to approximately 48 months
measure: Percentage of Participants With All Adverse Events Related to Treatment in the ITT Population
timeFrame: Baseline up to approximately 48 months
measure: Time to Deterioration (TTD) in Patient-Rported Lung Cancer Symptoms
timeFrame: Randomization up to approximately 48 months
measure: EORTC QLQ-C30 Score
timeFrame: 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
measure: EORTC QLQ-LC13 Score
timeFrame: 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
measure: EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index Based and Visual Analogue Scale (VAS) Scores
timeFrame: 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
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Changsha
country: China
facility: Hu Nan Provincial Cancer Hospital
city: Chengdu City
country: China
facility: Sichuan Cancer Hospital
city: Chongqing
country: China
facility: Southwest Hospital , Third Military Medical University
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Guangzhou City
country: China
facility: Sun Yet-sen University Cancer Center
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Hefei City
country: China
facility: Anhui Province Cancer Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Nanning
country: China
facility: Guangxi Cancer Hospital of Guangxi Medical University
city: Shanghai City
country: China
facility: Fudan University Shanghai Cancer Center; Medical Oncology
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Wuhan
country: China
facility: Tumor Center,Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
city: Xi'an
country: China
facility: First Affiliated Hospital of Medical College of Xi'an Jiaotong University
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: