A Study of Atezolizumab Administered in Combination With Bevacizumab and/or With Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01633970
First received: June 22, 2012
Last updated: April 2, 2016
Last verified: February 2016
  Purpose
This open-label, Phase Ib study that has six treatment arms is designed to assess the safety, pharmacology and preliminary efficacy of atezolizumab (MPDL3280A; an engineered anti-PDL1 antibody) administered with bevacizumab (Arm A) and with bevacizumab plus oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) (Arm B), with carboplatin and paclitaxel (Arm C), with carboplatin and pemetrexed (Arm D), with carboplatin and nab-paclitaxel (Arm E), and with nab-paclitaxel (Arm F) in participants with locally advanced or metastatic solid tumors. The study includes dose escalation cohort for establishing the maximum tolerated dose (MTD) or maximum administered dose (MAD) and then expansion cohort will be initiated based on a selected dose level at or below the MTD or MAD.

Condition Intervention Phase
Cancer
Drug: 5-FU
Drug: Atezolizumab
Drug: Bevacizumab
Drug: Carboplatin
Drug: Leucovorin
Drug: Nab-paclitaxel
Drug: Oxaliplatin
Drug: Paclitaxel
Drug: Pemetrexed
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib Study of the Safety and Pharmacology of Atezolizumab (Anti-PD-L1 Antibody) Administered With Bevacizumab and/or With Chemotherapy in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Maximum tolerated atezolizumab dose [ Time Frame: 21 days for Arms A, C, D and E and the 28 days following the first administration of atezolizumab in Arm B ] [ Designated as safety issue: Yes ]
  • Percentage of participants with adverse events [ Time Frame: approximately 5.25 years ] [ Designated as safety issue: No ]
  • Percentage of participants with dose-limiting toxicities [ Time Frame: 21 days for Arms A, C, D and E and the 28 days following the first administration of atezolizumab in Arm B ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics: Maximum serum concentration (Cmax) of atezolizumab [ Time Frame: Predose (0 hour), 0.5, 24 hour postdose on Cycle 1 Day 1, predose on, Cycle 1 Days 8, 15, Day 1 of Cycles 3, 4, and every 2 cycles thereafter until Cycle 16 and then every 8 cycles up to 120 days after end of treatment (approximately 5.25 years) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Minimum serum concentration (Cmin) of atezolizumab [ Time Frame: Predose (0 hour), 0.5, 24 hour postdose on Cycle 1 Day 1, predose on, Cycle 1 Days 8, 15, Day 1 of Cycles 3, 4, and every 2 cycles thereafter until Cycle 16 and then every 8 cycles up to 120 days after end of treatment (approximately 5.25 years) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Clearance of atezolizumab [ Time Frame: Predose (0 hour), 0.5, 24 hour postdose on Cycle 1 Day 1, predose on, Cycle 1 Days 8, 15, Day 1 of Cycles 3, 4, and every 2 cycles thereafter until Cycle 16 and then every 8 cycles up to 120 days after end of treatment (approximately 5.25 years) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Volume of distribution of atezolizumab [ Time Frame: Predose (0 hour), 0.5, 24 hour postdose on Cycle 1 Day 1, predose on, Cycle 1 Days 8, 15, Day 1 of Cycles 3, 4, and every 2 cycles thereafter until Cycle 16 and then every 8 cycles up to 120 days after end of treatment (approximately 5.25 years) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Accumulation ratio of atezolizumab [ Time Frame: Predose (0 hour), 0.5, 24 hour postdose on Cycle 1 Day 1, predose on, Cycle 1 Days 8, 15, Day 1 of Cycles 3, 4, and every 2 cycles thereafter until Cycle 16 and then every 8 cycles up to 120 days after end of treatment (approximately 5.25 years) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Half-life of atezolizumab [ Time Frame: Predose (0 hour), 0.5, 24 hour postdose on Cycle 1 Day 1, predose on, Cycle 1 Days 8, 15, Day 1 of Cycles 3, 4, and every 2 cycles thereafter until Cycle 16 and then every 8 cycles up to 120 days after end of treatment (approximately 5.25 years) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Area under the concentration-time curve of atezolizumab [ Time Frame: Predose (0 hour), 0.5, 24 hour postdose on Cycle 1 Day 1, predose on, Cycle 1 Days 8, 15, Day 1 of Cycles 3, 4, and every 2 cycles thereafter until Cycle 16 and then every 8 cycles up to 120 days after end of treatment (approximately 5.25 years) ] [ Designated as safety issue: No ]
  • Percentage of participants with best overall response according to RECIST criteria [ Time Frame: approximately 5.25 years ] [ Designated as safety issue: No ]
  • Percentage of participants with objective response (complete response + partial response) according to RECIST criteria [ Time Frame: approximately 5.25 years ] [ Designated as safety issue: No ]
  • Duration of objective response according to RECIST criteria [ Time Frame: approximately 5.25 months ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: approximately 5.25 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 225
Study Start Date: July 2012
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: Atezolizumab + Bevacizumab
Participants will receive intravenous (IV) bevacizumab (15 milligrams per kilogram [mg/kg]) on Day 1 of Cycle 1 followed by IV atezolizumab (1200 mg every 3 weeks [q3w]) after Days 5-7 and then atezolizumab (1200 mg q3w) and bevacizumab IV q3w on Day 1 of all subsequent cycles up to the end of treatment.
Drug: Atezolizumab
Participants will receive IV atezolizumab (800 mg q2w or 1200 mg q3w) q3w.
Other Name: MPDL3280A
Drug: Bevacizumab
Participants will receive bevacizumab 10 or 15 mg/kg IV q3w.
Other Name: Avastin
Experimental: B: Atezolizumab + Bevacizumab + FOLFOX
Participants will receive IV FOLFOX (oxaliplatin [85 milligrams per meter square {mg/m^2}], leucovorin [400 mg/m^2], 5-FU [400 mg/m^2]) on Day 1 of Cycle 1 and then IV atezolizumab (800 mg every 2 weeks [q2w]), bevacizumab (10 mg/kg) IV q3w and FOLFOX q2w on Day 1 of all subsequent cycles as per institutional guidelines.
Drug: 5-FU
Participants will receive 5-FU 400 mg/m^2 IV q2w.
Drug: Atezolizumab
Participants will receive IV atezolizumab (800 mg q2w or 1200 mg q3w) q3w.
Other Name: MPDL3280A
Drug: Bevacizumab
Participants will receive bevacizumab 10 or 15 mg/kg IV q3w.
Other Name: Avastin
Drug: Leucovorin
Participants will receive leucovorin 400 mg/m^2 IV q2w.
Drug: Oxaliplatin
Participants will receive oxaliplatin 85 mg/m^2 IV q2w.
Experimental: C: Atezolizumab + Carboplatin + Paclitaxel
Participants will receive IV atezolizumab (1200 mg q3w) in combination with paclitaxel IV (200 mg/m^2) q3w and then carboplatin IV q3w to achieve an initial target area under the curve (AUC) of 6 milligrams per milliters per minute (mg/mL/min).
Drug: Atezolizumab
Participants will receive IV atezolizumab (800 mg q2w or 1200 mg q3w) q3w.
Other Name: MPDL3280A
Drug: Carboplatin
Participants will receive carboplatin IV q3w with target AUC of 6 mg/mL.
Drug: Paclitaxel
Participants will receive paclitaxel 200 mg/m^2 IV q3w.
Experimental: D: Atezolizumab + Carboplatin + Pemetrexed
Participants will receive IV atezolizumab (1200 mg q3w) in combination with premetrexed IV (500 mg/m^2) q3w and then carboplatin IV q3w to achieve an initial target AUC of 6 mg/mL/min.
Drug: Atezolizumab
Participants will receive IV atezolizumab (800 mg q2w or 1200 mg q3w) q3w.
Other Name: MPDL3280A
Drug: Carboplatin
Participants will receive carboplatin IV q3w with target AUC of 6 mg/mL.
Drug: Pemetrexed
Participants will receive pemetrexed 500 mg/m^2 IV q3w.
Experimental: E: Atezolizumab + Carboplatin + Nab-paclitaxel
Participants will receive IV atezolizumab (1200 mg q3w) in combination with nab-paclitaxel IV (100 mg/m^2) once weekly (q1w) and then carboplatin IV q3w to achieve an initial target AUC of 6 mg/mL/min.
Drug: Atezolizumab
Participants will receive IV atezolizumab (800 mg q2w or 1200 mg q3w) q3w.
Other Name: MPDL3280A
Drug: Carboplatin
Participants will receive carboplatin IV q3w with target AUC of 6 mg/mL.
Drug: Nab-paclitaxel
Participants will receive nab-paclitaxel 100 mg/m^2 IV q1w.
Experimental: F: Atezolizumab + Nab-paclitaxel
Participants will receive IV atezolizumab (800 mg q2w) in combination with nab-paclitaxel IV (125 mg/m^2) q1w.
Drug: Atezolizumab
Participants will receive IV atezolizumab (800 mg q2w or 1200 mg q3w) q3w.
Other Name: MPDL3280A
Drug: Nab-paclitaxel
Participants will receive nab-paclitaxel 100 mg/m^2 IV q1w.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients greater than or equal to (>=) 18 years of age
  • Histologically or cytologically documented advanced solid tumors
  • Adequate hematologic and end organ function
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • 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

Eligible Tumor Types:

Arm A Escalation Cohorts/Arm A Biopsy Cohort/Arm B Biopsy Cohort (Cutaneous/Subcutaneous Lesions)

  • Histologically or cytologically documented, incurable or metastatic solid malignancy that has failed all available or acceptable standard therapy for which the patient is eligible Arm A Safety Expansion Cohort/Arm B Escalation Cohorts/Arm B Safety Expansion Cohort/Arm B Biopsy Cohort (Liver Lesions)
  • Histologically or cytologically confirmed metastatic colorectal cancer (CRC). Patients in the Arm A Safety Expansion Cohort must have mCRC for which established therapies have proved ineffective or intolerable. Patients with malignancies other than metastatic colorectal cancer (mCRC) within 5 years prior to Day 1 (except for those with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) are not eligible.

Arm A Safety Expansion Cohort

  • Up to 10 patients with CRC and high microsatellite instability (MSI-H) tumors will be enrolled.
  • Histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction for which established therapies have proved ineffective or intolerable The decision may be made to restrict enrollment to patients with a specified tumor PD-L1 status (e.g., immunohistochemistry [IHC] status 0/1 or 2/3).
  • Measurable/assessable ovarian cancer (defined as epithelial ovarian, fallopian tube, or primary peritoneal cancer) that has progressed <6 months after completing platinum-based therapy. The following histological types are eligible:

Adenocarcinoma NOS Clear cell adenocarcinoma Endometriod adenocarcinoma Malignant Brenner's tumour Mixed epithelial carcinoma Mucinous adenocarcinoma Serous adenocarcinoma Transitional cell carcinoma Undifferentiated carcinoma

Arm A renal cell carcinoma (RCC) Cohort:

- Histologically or cytologically confirmed advanced or metastatic RCC with a clear cell component.

Arms C, D, and E Cohorts:

- Histologically or cytologically documented Stage IIIB (not eligible for definitive chemoradiotherapy), Stage IV, or recurrent non-small cell lung cancer (NSCLC).

Arm F Cohort: - Histologically confirmed ER-, PR-, and HER-negative (triple-negative) adenocarcinoma of the breast (TNBC) that has been treated with systemic cytotoxic therapy. Locally recurrent disease must not be amenable to resection with curative intent. Patients with tumors amenable to excisional, punch, or core needle biopsy are eligible for a separate biopsy expansion cohort.

Tumor molecular status:

Arm A safety expansion cohort - Up to 10 patients with CRC and MSI-H may be enrolled

Exclusion Criteria:

  • Any approved anti-cancer therapy, including chemotherapy, hormonal therapy, radiotherapy, or herbal therapy intended as anti-cancer therapy, within 3 weeks prior to initiation of study treatment; the following are allowed: hormonal therapy with gonadotropin-releasing hormone agonists or antagonists for prostate cancer, hormone-replacement therapy, and palliative radiotherapy for bone metastases greater than (>) 2 weeks prior to Day 1
  • Bisphosphonate therapy for symptomatic hypercalcemia
  • Known clinically significant liver disease
  • Known primary central nervous (CNS) malignancy or active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
  • Pregnant or lactating women
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies or any component of the atezolizumab formulation
  • History of autoimmune disease
  • History of idiopathic pulmonary fibrosis
  • History of HIV or hepatitis C infection; history of hepatitis B is allowed if infection has resolved (absence of hepatitis B surface antigen [HBsAg])
  • Severe infections within 4 weeks prior to Day 1, or signs or symptoms of significant infection within 2 weeks prior to Day 1
  • Initiation of oral antibiotics less than (<) 14 days prior to Day 1
  • History of myocardial infarction, unstable angina or stroke with 6 months prior to Day 1
  • Administration of a live, attenuated vaccine within 4 weeks before Day 1 or anticipation that such a live attenuated vaccine will be required during the study
  • Any bevacizumab-specific exclusion criteria Exclusion Criteria Unique to Arm A RCC Cohort
  • Any prior systemic treatment (including tyrosine kinase inhibitors, antibody therapy, immunotherapy, chemotherapy, hormonal therapy, or investigational therapy) for RCC. All treatments, neo-adjuvant, adjuvant, or for locally advanced or metastatic RCC are not permitted.

Exclusion Criteria Unique to Arm A Gastric Cancer Cohort

- Prior approved or experimental anti-VEGF/VEGFR therapy (including, for example, bevacizumab or nintedanib). The decision may be made to allocate a specified number of slots to patients who have received prior anti-VEGF/VEGFR therapy.

Exclusion Criteria Unique to Arm A Ovarian Cancer Cohort Refractory disease History of bowel obstruction >2 prior anticancer regimens Prior approved or experimental anti-VEGF/VEGFR therapy (including, for example, bevacizumab or nintedanib) The decision may be made to allocate a specified number of slots to patients who have received prior anti-VEGF/VEGFR therapy.

Exclusion Criteria Unique to Arm B:

  • Prior treatment with an oxaliplatin-containing regimen. Oxaliplatin >12 months prior to the diagnosis of metastatic disease is permitted.
  • Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene polymorphism predisposing the patient for 5-FU toxicity.

Exclusion Criteria Unique to Arms C, D, and E:

  • Prior chemotherapy for locally advanced or metastatic NSCLC.
  • For patients who received prior adjuvant/neo-adjuvant chemotherapy or chemoradiation for NSCLC, a treatment-free interval >6 months between the last treatment administration and the date of recurrence in required.
  • Patients with a known epidermal growth factor receptor (EGFR) sensitizing mutation must have experienced disease progression during or after treatment with an approved EGFR tyrosine kinase inhibitor.
  • Patients with a known anaplastic lymphoma kinase (ALK) fusion oncogene must have experienced disease progression during or after treatment with crizotinib.
  • For Arm D (carboplatin + pemetrexed), squamous cell histology or evidence of mixed NSCLC histology with a predominance of the squamous cell type.
  • For Arm D (carboplatin + pemetrexed), inability to discontinue treatment with non-steroidal anti-inflammatory drugs (NSAIDs) for 5 days.

Exclusion Criteria Unique to Arm F:

  • Prior therapy with more than two cytotoxic regimens for metastatic or locally advanced triple-negative breast cancer (TNBC)
  • Treatment with a taxane-containing regimen within 6 months before enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01633970

Contacts
Contact: Reference Study ID Number: GP28328 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
United States, Colorado
Recruiting
Aurora, Colorado, United States, 80045
United States, Connecticut
Recruiting
New Haven, Connecticut, United States, 06520-8063
United States, District of Columbia
Recruiting
Washington, District of Columbia, United States, 20057
United States, Illinois
Recruiting
Chicago, Illinois, United States, 60637
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States, 02114
Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Recruiting
New York, New York, United States, 10016
United States, North Carolina
Recruiting
Durham, North Carolina, United States, 27705
Recruiting
Huntersville, North Carolina, United States, 28078
United States, Tennessee
Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01633970     History of Changes
Other Study ID Numbers: GP28328  2012-001422-10 
Study First Received: June 22, 2012
Last Updated: April 2, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech, Inc.:
PD-L1
PD-1
PDL1
antiPD-L1
atezolizumab
Solid tumor
MPDL320A
MPDL3280A
Colorectal
CRC
gastric
ovarian

Additional relevant MeSH terms:
Paclitaxel
Oxaliplatin
Albumin-Bound Paclitaxel
Bevacizumab
Carboplatin
Pemetrexed
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Immunologic Factors

ClinicalTrials.gov processed this record on August 23, 2016