A Study of the Safety and Efficacy of Atezolizumab Administered in Combination With Bevacizumab and/or Other Treatments in Participants With Solid Tumors

NCT02715531 | Completed Phase 1

• 1 other identifier: GO30140
• Study Type: interventional
• Target: 243
• Locations: 7 countries
• Sites: 30

Brief Summary

This study will evaluate the safety, efficacy, and pharmacokinetics of atezolizumab in combination with bevacizumab, bevacizumab + oxaliplatin, leucovorin and 5-fluorouracil (5-FU) (FOLFOX), vanucizumab, nab-paclitaxel + gemcitabine, FOLFOX, or 5-FU + cisplatin, in participants with solid tumors.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Number of Participants With At Least One Adverse Event, with Severity Determined According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)

  From screening to up to 90 days after the last dose of study drug (up to approximately 55 months)

• Percentage of Participants with Objective Response as Determined By The Independent Review Facility (IRF) According To Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (Arm A)

  From screening to end of study (approximately 55 months)

• Progression-Free Survival (PFS) as determined by the Independent Review Facility (IRF) according to RECIST v 1.1 (Arm F)

  From randomization to the first occurrence of disease progression or death from any cause (whichever occurs first)

Secondary Outcomes (21)

• Serum Concentrations of Atezolizumab (All Arms)

  Predose (0 hour[h]), 30 minutes(min) postdose on Day 1 of Cycles(Cy) 1 and 3; Predose(0h) on Day 1 of Cy 2,4,8 and every 8 Cy until treatment discontinuation (up to 55 months); 120 days after last dose (Cy length=21-28 days; up to 55 months)

• Serum Concentrations of Bevacizumab (Arm A, Arm B and Group F1)

  Predose (0 h) and 30 min postdose (infusion length=30-90 min) on Day 1 of Cy 1 and 3; at treatment discontinuation (up to 55 months); at 120 days after last dose (Cy length=21-28 days; up to 55 months)

• Plasma Concentration of Oxaliplatin (Arm B and Group E1)

  Predose (0 h) and 5-10 min before the end of infusion (infusion length=120 min) on Day 1 of Cycles 1 and 3 (Cycle length=21-28 days; up to approximately 3 months)

• Plasma Concentration of 5-FU (Arm B and Arm E)

  Predose (0 h), immediately following bolus administration and 2 hours post-bolus dose on Day 1 of Cycles 1 and 3 (Cycle length=21-28 days; up to approximately 3 months)

• Plasma Concentration of Cisplatin (Group E2)

  Predose (0 h) and 5-10 minutes before the end of infusion (infusion length=120 min) on Day 1 of Cycles 1 and 3 (Cycle length=21 days; up to approximately 3 months)

Study Arms (5)

Arm A (Hepatocellular Carcinoma [HCC], All subtypes)

EXPERIMENTAL

Participants with advanced or metastatic and/or unresectable HCC who have received no prior treatment are non-randomized and will receive atezolizumab and bevacizumab, every 3 weeks (q3w), each cycle of 21 days, as long as participants are experiencing clinical benefit in the opinion of the investigator.

Drug: Atezolizumab; Drug: Bevacizumab

Arm B (Gastric Cancer)

EXPERIMENTAL

Participants with previously untreated human epidermal growth factor receptor 2 (HER2)-negative adenocarcinoma of the stomach or gastroesophageal junction (GEJ) are non-randomized and will receive atezolizumab, bevacizumab, and FOLFOX (oxaliplatin, leucovorin, and 5-fluorouracil \[FU\]), every 2 weeks (q2w), each cycle of 28 days, as long as participants are experiencing clinical benefit in the opinion of the investigator. Oxaliplatin will be administered for up to 8 cycles. After 6 months, at discretion of investigator, capecitabine may be administered as maintenance therapy without oxaliplatin instead of infusional 5-FU and leucovorin, and biologic therapy may be given every 3 weeks (q3w). In the event that a patient experiences unacceptable toxicity after replacement of infusional 5-FU and leucovorin with capecitabine, the patient may be allowed to switch back to 5-FU and leucovorin following investigator discussion with the Medical Monitor.

Drug: 5-FU; Drug: Atezolizumab; Drug: Bevacizumab; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Capecitabine

Arm C (Metastatic Pancreatic Cancer)

EXPERIMENTAL

Participants with previously untreated metastatic pancreatic cancer are non-randomized and will receive atezolizumab q2w starting on Day 1, Cycle 1 (each cycle of 28 days). Administration of nab-paclitaxel followed by gemcitabine will occur on Days 1, 8, and 15 of each cycle (3-weeks-on/1-week-off schedule). Treatment consisting of atezolizumab with gemcitabine and nab-paclitaxel may be continued as long as participants are experiencing clinical benefit in the opinion of the investigator.

Drug: Atezolizumab; Drug: Gemcitabine; Drug: Nab-Paclitaxel

Arm E (Randomized Metastatic Esophageal Cancer)

EXPERIMENTAL

Participants with squamous metastatic esophageal cancer (mEC) will be randomized (1:1) into Group E1 and Group E2. All participants with metastatic adenocarcinoma of esophageal carcinoma or GEJ Siewert Classification Type I will be enrolled into Group E3. In Groups E1 and E3, participants will receive atezolizumab and FOLFOX, q2w, each cycle of 28 days, as long as participants are experiencing clinical benefit in opinion of the investigator. Oxaliplatin will be administered for up to 8 cycles. In Group E2, participants will receive atezolizumab followed by cisplatin and 5-FU q3w. Cisplatin will be administered for up to 6 cycles. Treatment with atezolizumab in combination with 5-FU may be continued as long as participants experience clinical benefit in opinion of the investigator.

Drug: 5-FU; Drug: Atezolizumab; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Cisplatin

Arm F (Randomized HCC)

EXPERIMENTAL

Participants with advanced or metastatic and/or unresectable HCC who have received no prior systemic treatment will be randomized (1:1) into Group F1 and Group F2. Participants will receive atezolizumab alone (Group F2) or combined with bevacizumab (Group F1) on a q3w schedule, with dosing on Day 1 of each 21 day Cycle. Treatment with atezolizumab with or without bevacizumab may be continued as long as participants are experiencing clinical benefit in the opinion of the investigator. Participants who are randomly assigned to Group F2 (atezolizumab monotherapy) and experience investigator-assessed unequivocal radiographic progression as per RECIST v1.1 will also be given the option to cross over to atezolizumab and bevacizumab combination therapy, provided they meet the criteria for crossover and Medical Monitor approval is obtained.

Drug: Atezolizumab; Drug: Bevacizumab

Interventions

5-FU DRUG

5-FU (400 mg/m\^2) will be administered as an IV bolus, followed by 2400 mg/m\^2 by continuous IV infusion over 46 (± 1) hours, q2w.

Arm B (Gastric Cancer); Arm E (Randomized Metastatic Esophageal Cancer)

Atezolizumab DRUG

Participants will receive atezolizumab in a flat dose of 1200 mg q3w (Arm A, Group E2, and Arm F) or 840 mg q2w (Arm B, Arm C, and Groups E1 and E3).

Also known as: Tecentriq; RO5541267

Arm A (Hepatocellular Carcinoma [HCC], All subtypes); Arm B (Gastric Cancer); Arm C (Metastatic Pancreatic Cancer); Arm E (Randomized Metastatic Esophageal Cancer); Arm F (Randomized HCC)

Bevacizumab DRUG

Participants will receive bevacizumab at 15 mg/kg q3w (Arm A and Group F1) or 10 mg/kg q2w (Arm B).

Arm A (Hepatocellular Carcinoma [HCC], All subtypes); Arm B (Gastric Cancer); Arm F (Randomized HCC)

Gemcitabine DRUG

Gemcitabine will be administered according to the local prescribing information. The starting dose-level of gemcitabine (1000 mg/m\^2) will be administered intravenously over 35 (± 5) minutes on Days 1, 8, and 15 of each 28-day cycle (3-weeks-on/1-week-off schedule).

Arm C (Metastatic Pancreatic Cancer)

Leucovorin DRUG

Leucovorin 200 mg/m\^2 L-isomer form or 400 mg/m\^2 D,L-racemic form will be administered IV over 120 (± 15) minutes, q2w.

Arm B (Gastric Cancer); Arm E (Randomized Metastatic Esophageal Cancer)

Nab-Paclitaxel DRUG

Nab-Paclitaxel will be administered according to the local prescribing information. The starting dose-level of nab-paclitaxel (125 mg/m\^2) will be administered intravenously over 35 (± 5) minutes on Days 1, 8, and 15 of each 28-day cycle (3-weeks-on/1-week-off schedule).

Arm C (Metastatic Pancreatic Cancer)

Oxaliplatin DRUG

Oxaliplatin 85 mg/m\^2 will be administered IV over 120 (± 5) minutes q2w.

Arm B (Gastric Cancer); Arm E (Randomized Metastatic Esophageal Cancer)

Capecitabine DRUG

Capecitabine may be administered after 6 months at the discretion of the investigator (range of 650-1000 mg/m\^2) twice daily on Days 1-4 of a 21-day cycle.

Arm B (Gastric Cancer)

Cisplatin DRUG

Cisplatin will be administered as 80 mg/m\^2 IV over 120 minutes q3w (Group E2).

Arm E (Randomized Metastatic Esophageal Cancer)

Eligibility Criteria

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

You may qualify if:

• Measurable disease per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate hematologic and end organ function
• Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to Grade less than or equal to (\</=) 1 prior to study entry, with the exception of alopecia
• Ready to use reliable contraceptive procedures
• Participants with advanced or metastatic and/or unresectable HCC
• The participant has disease that is not amenable to a curative approach
• No prior line of systemic therapy (includes participants who are sorafenib-naïve)
• Willing to undergo fresh liver biopsy if provided archival tissue was taken greater than (\>) 6 months from Cycle 1 Day 1
• Child-Pugh Score of up to B7
• Serum bilirubin \</= 3 times upper limit of normal (x ULN)
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) \</= 2 x ULN
• Albumin \>2.8 grams per deciliter (g/dL)
• Documented virology status of hepatitis, as confirmed by screening hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and/or anti-hepatitis C virus (anti-HCV)
• Antiviral therapy per local standard-of-care if active hepatitis B virus (HBV)

You may not qualify if:

• Uncontrolled pleural effusion, pericardial effusion, or ascites
• Uncontrolled tumor-related pain
• Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease (exception for participants in Arm A and Arm F)
• Known primary central nervous system (CNS) malignancy or untreated or active CNS metastases
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or other recombinant human antibodies
• Positive test for Human Immunodeficiency Virus (HIV)
• Active hepatitis B (chronic or acute), or hepatitis C (exception for participants in Arm A and Arm F)
• Active tuberculosis
• Severe infections within 4 weeks prior to Day 1
• Signs or symptoms of significant infection within 2 weeks prior to Day 1
• Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
• Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to Day 1, unstable arrhythmias, or unstable angina
• History of stroke, reversible ischemic neurological defect or transient ischemic attack within 6 months prior to Day 1
• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (30)

Stanford Cancer Institute; Hematology

Palo Alto, California, 94305, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Columbia University Medical Center

New York, New York, 10027, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27514, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

Sarah Cannon Research Inst.

Nashville, Tennessee, 37203, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Monash Medical Centre Clayton

Clayton, Victoria, 3168, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

The 81st Hospital of P.L.A.

Nanjing, 210002, China

Location

National Cancer Center Hospital East

Chiba, 277-8577, Japan

Location

Yokohama City University Medical Center

Kanagawa, 232-0024, Japan

Location

Kanagawa Cancer Center

Kanagawa, 241-8515, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Seoul National University Bundang Hospital

Seongnam-si, 13605, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06531, South Korea

Location

China Medical University Hospital

North Dist., 40402, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70457, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Chang Gung Medical Foundation - LINKOU; Dept of Cardiology

Taoyuan, 00333, Taiwan

Location

Related Publications (1)

• Lee MS, Ryoo BY, Hsu CH, Numata K, Stein S, Verret W, Hack SP, Spahn J, Liu B, Abdullah H, Wang Y, He AR, Lee KH; GO30140 investigators. Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. Lancet Oncol. 2020 Jun;21(6):808-820. doi: 10.1016/S1470-2045(20)30156-X.

  PMID: 32502443 DERIVED

MeSH Terms

Interventions

Fluorouracil; atezolizumab; Bevacizumab; Gemcitabine; Leucovorin; 130-nm albumin-bound paclitaxel; Oxaliplatin; Capecitabine; Cisplatin

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2016
• First Posted: March 22, 2016
• Study Start: April 6, 2016
• Primary Completion: May 31, 2021
• Study Completion: May 31, 2021
• Last Updated: July 9, 2021

Record last verified: 2021-07

Locations

CN (1); NZ (1); AU (2); JP (4); KR (5); TW (5); US (12)