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

Conditions

• Solid Tumor

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

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.
• 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).
• Bevacizumab — DRUG
  Participants will receive bevacizumab at 15 mg/kg q3w (Arm A and Group F1) or 10 mg/kg q2w (Arm B).
• 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).
• 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.
• 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).
• Oxaliplatin — DRUG
  Oxaliplatin 85 mg/m\^2 will be administered IV over 120 (± 5) minutes q2w.
• 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.
• Cisplatin — DRUG
  Cisplatin will be administered as 80 mg/m\^2 IV over 120 minutes q3w (Group E2).

Study Details

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.

Key Dates

Start date

Apr 6, 2016

Status verified

Jul 2021

Primary completion

May 31, 2021

Completion

May 31, 2021

Study Design

Enrollment

243 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

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

Primary Outcome Measure

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) [ Time Frame: From screening to up to 90 days after the last dose of study drug (up to approximately 55 months) ]

Locations (12)

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