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

NCT04028050 | Completed Phase 3

• 1 other identifier: ML41118
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 25

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.

Conditions

Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of Serious Adverse Events

  4 weeks after last dose of study treatment

• Incidence of Serious and Non-Serious Immune Mediated Adverse Events

  4 weeks after last dose of study treatment

Secondary Outcomes (7)

• Overall Survival (OS) Rate at 1 Year

  1 Year

• Overall Survival (OS) Rate at 2 Years

  2 Years

• Overall Survival (OS) Rate at 3 Years

  3 Years

• Overall Survival (OS) Rate

  Up to approximately 54 months

• Progression-Free Survival (PFS)

  Up to approximately 54 months

Study Arms (1)

Atezolizumab + Carboplatin + Etoposide

EXPERIMENTAL

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; Drug: Carboplatin; Drug: Etoposide

Interventions

Atezolizumab DRUG

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.

Also known as: MPDL3280A, RO5541267, Tecentriq

Atezolizumab + Carboplatin + Etoposide

Carboplatin DRUG

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.

Atezolizumab + Carboplatin + Etoposide

Etoposide DRUG

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.

Atezolizumab + Carboplatin + Etoposide

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (25)

Presidio Ospedaliero Vito Fazzi; Unita Operativa Di Oncologia Medica

Lecce, Apulia, 73044, Italy

Location

Ist. Ricovero e Cura a Carattere Scientifico-Centro Rif. Oncologico della Basilica

Rionero in Vulture (PZ), Basilicate, 85028, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati

Avellino, Campania, 83100, Italy

Location

Az. Osp. Monaldi; 2 Pneumologia-Chemioterapia E Day Hospital-Pneumoncologia

Napoli, Campania, 80131, Italy

Location

Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica

Napoli, Campania, 80131, Italy

Location

Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale

Napoli, Campania, 80131, Italy

Location

Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica

Bologna, Emilia-Romagna, 40138, Italy

Location

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica

Meldola, Emilia-Romagna, 47014, Italy

Location

Centro Di Riferimento Oncologico; Struttura Operativa Complessa Di Oncologia Medica B

Aviano, Friuli Venezia Giulia, 33081, Italy

Location

Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica

Rome, Lazio, 00128, Italy

Location

Policlinico Universitario Agostino Gemelli

Rome, Lazio, 00168, Italy

Location

Azienda Ospedaliera San Camillo Forlanini

Rome, Lazio, 151, Italy

Location

ASL 3 Genovese

Genoa, Liguria, 16125, Italy

Location

ASST Spedali Civili di Brescia

Brescia, Lombardy, 25123, Italy

Location

Ospedale San Raffaele S.r.l.

Milan, Lombardy, 20132, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy

Location

Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia

Milan, Lombardy, 20141, Italy

Location

A.O.U. Maggiore della Carità

Novara, Piedmont, 28100, Italy

Location

Azienda Unita Sanitaria Locale N1 Sassari; Unita Operativa Di Oncologia Medica

Sassari, Sardinia, 07100, Italy

Location

Azienda Ospedaliera Vincenzo Cervello

Palermo, Sicily, 90127, Italy

Location

Ospedale San Vincenzo Taormina :Divisione di Oncologia Medica

Taormina, Sicily, 98039, Italy

Location

Ospedali Riuniti Di Ancona; Oncology

Ancona, The Marches, 60121, Italy

Location

Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; Dipartimento Cardio Toraco Vascolare

Pisa, Tuscany, 56124, Italy

Location

ULSS2 Marca Trevigiana; UOC Oncologia Medica - Distretto di Treviso

Treviso, Veneto, 31100, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona; UOC Oncologia

Verona, Veneto, 37126, Italy

Location

Related Publications (1)

• Bria E, Morgillo F, Garassino MC, Ciardiello F, Ardizzoni A, Stefani A, Verderame F, Morabito A, Chella A, Tonini G, Gilli M, Del Signore E, Berardi R, Mencoboni M, Bearz A, Delmonte A, Migliorino MR, Gridelli C, Pazzola A, Iero M, De Marinis F. Atezolizumab Plus Carboplatin and Etoposide in Patients with Untreated Extensive-Stage Small-Cell Lung Cancer: Interim Results of the MAURIS Phase IIIb Trial. Oncologist. 2024 May 3;29(5):e690-e698. doi: 10.1093/oncolo/oyad342.

  PMID: 38377176 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

atezolizumab; Carboplatin; Etoposide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2019
• First Posted: July 22, 2019
• Study Start: August 12, 2019
• Primary Completion: July 13, 2023
• Study Completion: July 13, 2023
• Last Updated: July 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share

Locations

IT (25)