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出境医 / 临床实验 / A Study of Atezolizumab in Combination With Carboplatin Plus Etoposide to Investigate Safety and Efficacy in Patients With Untreated Extensive-Stage Small Cell Lung Cancer (MAURIS)

A Study of Atezolizumab in Combination With Carboplatin Plus Etoposide to Investigate Safety and Efficacy in Patients With Untreated Extensive-Stage Small Cell Lung Cancer (MAURIS)

Study Description
Brief Summary:
This is a phase IIIB, single-arm, single-country, multicenter study of the safety and efficacy of atezolizumab in combination with carboplatin plus etoposide in patients who have ES-SCLC and are chemotherapy-naive for their extensive-stage disease.

Condition or disease Intervention/treatment Phase
Small Cell Lung Carcinoma Drug: Atezolizumab Drug: Carboplatin Drug: Etoposide Phase 3

Detailed Description:
Induction treatment will be administered on a 21-day cycle for four/six cycles. Following the induction phase, participants will continue maintenance therapy with atezolizumab. Maintenance with atezolizumab will continue until disease progression (PD), unacceptable toxicity or loss of clinical benefit.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 155 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IIIB, Single Arm, Multicenter Study of Atezolizumab (Tecentriq) in Combination With Carboplatin Plus Etoposide to Investigate Safety and Efficacy in Patients With Untreated Extensive-Stage Small Cell Lung Cancer - MAURIS
Actual Study Start Date : August 12, 2019
Estimated Primary Completion Date : December 30, 2022
Estimated Study Completion Date : December 30, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: Atezolizumab + Carboplatin + Etoposide
Participants will receive intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min), followed by intravenous infusion of etoposide 100 milligrams per square meter (mg/m^2) on days 1 through 3 of each cycle during the induction phase (21-day cycle for four/six cycles). On Days 2 and 3, participants will receive etoposide alone. After the induction phase, participants will begin maintenance therapy with atezolizumab every 3 weeks until PD, unacceptable toxicity, loss of clinical benefit or study termination by the Sponsor.
 Drug: Atezolizumab
Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator. After the induction phase, participants will begin maintenance therapy with atezolizumab every 3 weeks.
Other Name: MPDL3280A, RO5541267, Tecentriq

Drug: Carboplatin
Carboplatin will be administered after completion of atezolizumab by IV infusion over 30-60 minutes to achieve an initial target AUC of 5 mg/mL/min (Calvert formula dosing) with standard anti-emetics per local practice guidelines.

Drug: Etoposide
Etoposide will be administered by IV infusion over 60 minutes following carboplatin administration, during the induction phase on Day 1 through 3 of each cycle. On Days 2 and 3, patients will receive etoposide alone.
Outcome Measures
Primary Outcome Measures :
  1. Incidence of Serious Adverse Events [ Time Frame: 4 weeks after last dose of study treatment ]
  2. Incidence of Serious and Non-Serious Immune Mediated Adverse Events [ Time Frame: 4 weeks after last dose of study treatment ]

Secondary Outcome Measures :
  1. Overall Survival (OS) Rate at 1 Year [ Time Frame: 1 Year ]
    OS at 1 year, defined as the proportion of participants remaining alive at 1 year after initiation of study treatment.

  2. Overall Survival (OS) Rate at 2 Years [ Time Frame: 2 Years ]
    OS at 2 years, defined as the proportion of participants remaining alive at 2 years after initiation of study treatment.

  3. Overall Survival (OS) Rate [ Time Frame: Up to approximately 42 months ]
    OS, defined as the time from initiation of study treatment to death from any cause

  4. Progression-Free Survival (PFS) [ Time Frame: Up to approximately 42 months ]
    PFS, defined as the time from initiation of study treatment 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 Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

  5. Objective response rate (ORR) [ Time Frame: Up to approximately 42 months ]
    ORR, defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.

  6. Duration of Response (DOR) [ Time Frame: Up to approximately 42 months ]
    Duration of response (DOR), defined as the time from initial response to disease progression or death among patients who have experienced a CR or PR (unconfirmed) during the study. Duration of response will be calculated based on disease status evaluated by the investigator according to RECIST v1.1.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed ES-SCLC per the Veterans Administration Lung Study Group (VALG) staging system
  • Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site since radiation and the previously irradiated lesion is not the only site of disease
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) from 0 to 2
  • Life expectancy > 12 weeks
  • No prior systemic treatment for ES-SCLC
  • Patients who have received prior chemoradiotherapy for limited-stage SCLC must have been treated with curative intent and experienced a treatment-free interval of at least 6 months since last chemotherapy, radiotherapy, or chemoradiotherapy cycle from diagnosis of ES-SCLC
  • Patients where thoracic radiotherapy (consolidation RT) is clinically indicated could be enrolled providing they receive RT between the completion of induction phase and the beginning of maintenance phase
  • Patients with Paraneoplastic syndromes can be enrolled if an autoimmune origin can be excluded
  • Adequate hematologic and end organ function
  • Negative human immunodeficiency virus (HIV) test at screening
  • Negative hepatitis B surface antigen (HBsAg) test at screening
  • Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
  • Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
  • For women of childbearing potential: agreement to remain abstinent or use of contraception
  • For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm

Exclusion Criteria:

  • Symptomatic or actively progressing central nervous system (CNS) metastases. Asymptomatic patients with treated or untreated CNS lesions are eligible, provided that all of the following criteria are met: (1) Measurable disease, per RECIST v1.1, must be present outside the CNS. (2) Patient has no history of intracranial hemorrhage or spinal cord hemorrhage. (3) Patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment. (4) Patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted. Metastases are limited to the cerebellum or the supratentorial region. (5) There is no evidence of interim progression between completion of CNS directed therapy and initiation of study treatment. (6) Asymptomatic patients with CNS metastases newly detected at screening are allowed at Investigator's discretion with no need to repeat the screening brain scan.
  • History of leptomeningeal disease
  • Uncontrolled tumor-related pain
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. Patients with indwelling catheters are allowed regardless of drainage frequency.
  • Uncontrolled or symptomatic hypercalcemia
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computerized tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Active tuberculosis
  • Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  • Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
  • History of malignancy other than SCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
  • Prior allogeneic stem cell or solid organ transplantation treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
  • Current treatment with anti-viral therapy for HBV
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
Contacts and Locations

Locations
Show Show 25 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche
Tracking Information
First Submitted Date  ICMJE July 19, 2019
First Posted Date  ICMJE July 22, 2019
Last Update Posted Date April 9, 2021
Actual Study Start Date  ICMJE August 12, 2019
Estimated Primary Completion Date December 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2020)
  • Incidence of Serious Adverse Events [ Time Frame: 4 weeks after last dose of study treatment ]
  • Incidence of Serious and Non-Serious Immune Mediated Adverse Events [ Time Frame: 4 weeks after last dose of study treatment ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 19, 2019)
  • Incidence of Serious Adverse Events [ Time Frame: 4 weeks after last dose of study treatment ]
  • Incidence of Serious and Non-Serious Immune Related Adverse Events [ Time Frame: 4 weeks after last dose of study treatment ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2019)
  • Overall Survival (OS) Rate at 1 Year [ Time Frame: 1 Year ]
    OS at 1 year, defined as the proportion of participants remaining alive at 1 year after initiation of study treatment.
  • Overall Survival (OS) Rate at 2 Years [ Time Frame: 2 Years ]
    OS at 2 years, defined as the proportion of participants remaining alive at 2 years after initiation of study treatment.
  • Overall Survival (OS) Rate [ Time Frame: Up to approximately 42 months ]
    OS, defined as the time from initiation of study treatment to death from any cause
  • Progression-Free Survival (PFS) [ Time Frame: Up to approximately 42 months ]
    PFS, defined as the time from initiation of study treatment 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 Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
  • Objective response rate (ORR) [ Time Frame: Up to approximately 42 months ]
    ORR, defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.
  • Duration of Response (DOR) [ Time Frame: Up to approximately 42 months ]
    Duration of response (DOR), defined as the time from initial response to disease progression or death among patients who have experienced a CR or PR (unconfirmed) during the study. Duration of response will be calculated based on disease status evaluated by the investigator according to RECIST v1.1.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Atezolizumab in Combination With Carboplatin Plus Etoposide to Investigate Safety and Efficacy in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
Official Title  ICMJE A Phase IIIB, Single Arm, Multicenter Study of Atezolizumab (Tecentriq) in Combination With Carboplatin Plus Etoposide to Investigate Safety and Efficacy in Patients With Untreated Extensive-Stage Small Cell Lung Cancer - MAURIS
Brief Summary This is a phase IIIB, single-arm, single-country, multicenter study of the safety and efficacy of atezolizumab in combination with carboplatin plus etoposide in patients who have ES-SCLC and are chemotherapy-naive for their extensive-stage disease.
Detailed Description Induction treatment will be administered on a 21-day cycle for four/six cycles. Following the induction phase, participants will continue maintenance therapy with atezolizumab. Maintenance with atezolizumab will continue until disease progression (PD), unacceptable toxicity or loss of clinical benefit.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Small Cell Lung Carcinoma
Intervention  ICMJE
  • Drug: Atezolizumab
    Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator. After the induction phase, participants will begin maintenance therapy with atezolizumab every 3 weeks.
    Other Name: MPDL3280A, RO5541267, Tecentriq
  • Drug: Carboplatin
    Carboplatin will be administered after completion of atezolizumab by IV infusion over 30-60 minutes to achieve an initial target AUC of 5 mg/mL/min (Calvert formula dosing) with standard anti-emetics per local practice guidelines.
  • Drug: Etoposide
    Etoposide will be administered by IV infusion over 60 minutes following carboplatin administration, during the induction phase on Day 1 through 3 of each cycle. On Days 2 and 3, patients will receive etoposide alone.
Study Arms  ICMJE Experimental: Atezolizumab + Carboplatin + Etoposide
Participants will receive intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min), followed by intravenous infusion of etoposide 100 milligrams per square meter (mg/m^2) on days 1 through 3 of each cycle during the induction phase (21-day cycle for four/six cycles). On Days 2 and 3, participants will receive etoposide alone. After the induction phase, participants will begin maintenance therapy with atezolizumab every 3 weeks until PD, unacceptable toxicity, loss of clinical benefit or study termination by the Sponsor.
Interventions:
  • Drug: Atezolizumab
  • Drug: Carboplatin
  • Drug: Etoposide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 7, 2021) 		155
Original Estimated Enrollment  ICMJE
 (submitted: July 19, 2019) 		150
Estimated Study Completion Date  ICMJE December 30, 2022
Estimated Primary Completion Date December 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed ES-SCLC per the Veterans Administration Lung Study Group (VALG) staging system
  • Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site since radiation and the previously irradiated lesion is not the only site of disease
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) from 0 to 2
  • Life expectancy > 12 weeks
  • No prior systemic treatment for ES-SCLC
  • Patients who have received prior chemoradiotherapy for limited-stage SCLC must have been treated with curative intent and experienced a treatment-free interval of at least 6 months since last chemotherapy, radiotherapy, or chemoradiotherapy cycle from diagnosis of ES-SCLC
  • Patients where thoracic radiotherapy (consolidation RT) is clinically indicated could be enrolled providing they receive RT between the completion of induction phase and the beginning of maintenance phase
  • Patients with Paraneoplastic syndromes can be enrolled if an autoimmune origin can be excluded
  • Adequate hematologic and end organ function
  • Negative human immunodeficiency virus (HIV) test at screening
  • Negative hepatitis B surface antigen (HBsAg) test at screening
  • Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
  • Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
  • For women of childbearing potential: agreement to remain abstinent or use of contraception
  • For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm

Exclusion Criteria:

  • Symptomatic or actively progressing central nervous system (CNS) metastases. Asymptomatic patients with treated or untreated CNS lesions are eligible, provided that all of the following criteria are met: (1) Measurable disease, per RECIST v1.1, must be present outside the CNS. (2) Patient has no history of intracranial hemorrhage or spinal cord hemorrhage. (3) Patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment. (4) Patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted. Metastases are limited to the cerebellum or the supratentorial region. (5) There is no evidence of interim progression between completion of CNS directed therapy and initiation of study treatment. (6) Asymptomatic patients with CNS metastases newly detected at screening are allowed at Investigator's discretion with no need to repeat the screening brain scan.
  • History of leptomeningeal disease
  • Uncontrolled tumor-related pain
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. Patients with indwelling catheters are allowed regardless of drainage frequency.
  • Uncontrolled or symptomatic hypercalcemia
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computerized tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Active tuberculosis
  • Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  • Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
  • History of malignancy other than SCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
  • Prior allogeneic stem cell or solid organ transplantation treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
  • Current treatment with anti-viral therapy for HBV
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04028050
Other Study ID Numbers  ICMJE ML41118
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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