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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 November 2016 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01633970
First received: June 22, 2012
Last updated: November 1, 2016
Last verified: November 2016

June 22, 2012
November 1, 2016
July 2012
December 2018   (final data collection date for primary outcome measure)
  • Maximum Tolerated Atezolizumab Dose [ Time Frame: Days 1-21 of Cycle 1 (Cycle length = 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: From Baseline up to 90 days after last dose of study drug or until initiation of another anti-cancer therapy (up to approximately 5 years) ] [ Designated as safety issue: No ]
  • Percentage of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: Days 1-21 of Cycle 1 (Cycle length = 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 ]
  • Safety: Incidence of adverse events [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Dose-limiting toxicities/maximum tolerated dose [ Time Frame: 21 days for Arm A and the 28 days following the first administration of MPDL3280A in Arm B ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01633970 on ClinicalTrials.gov Archive Site
  • Duration of Objective Response According to irRC [ Time Frame: From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years) ] [ Designated as safety issue: No ]
  • Progression-Free Survival According to RECIST v1.1 [ Time Frame: From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years) ] [ Designated as safety issue: No ]
  • Progression-Free Survival According to irRC [ Time Frame: Baseline until death or disease progression, whichever occurs first (up to approximately 5 years) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) of Atezolizumab [ Time Frame: Pre-infusion (0 hour [hr]) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Pre-infusion (0 hr) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Minimum Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Pre-infusion (0 hr) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Percentage of Participants With Best Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years) ] [ Designated as safety issue: No ]
  • Percentage of Participants With Best Overall Response According to Immune-Related Response Criteria (irRC) [ Time Frame: From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years) ] [ Designated as safety issue: No ]
  • Percentage of Participants With Objective Response (Complete Response + Partial Response) According to RECIST v1.1 [ Time Frame: From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years) ] [ Designated as safety issue: No ]
  • Percentage of Participants With Objective Response (Complete Response + Partial Response) According to irRC [ Time Frame: From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years) ] [ Designated as safety issue: No ]
  • Duration of Objective Response According to RECIST v1.1 [ Time Frame: From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Clearance of Atezolizumab [ Time Frame: Pre-infusion (0 hr) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Volume of Distribution of Atezolizumab [ Time Frame: Pre-infusion (0 hr) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Accumulation Ratio of Atezolizumab [ Time Frame: Pre-infusion (0 hr) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Half-Life of Atezolizumab [ Time Frame: Pre-infusion (0 hr) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Cmax of Bevacizumab [ Time Frame: Pre-infusion (0 hr), 0.5 hrs after EOI (infusion duration=90 min) on Day 1 Cycles 1 & 3 (each cycle = 21 days); EOT; every 30 days (for up to 120 days) after EOT until death or withdrawal or study closure (up to approximately 5 years) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Cmin of Bevacizumab [ Time Frame: Pre-infusion (0 hr), 0.5 hrs after EOI (infusion duration=90 min) on Day 1 Cycles 1 & 3 (each cycle = 21 days); EOT; every 30 days (for up to 120 days) after EOT until death or withdrawal or study closure (up to approximately 5 years) ] [ Designated as safety issue: No ]
  • Maximum Plasma Concentration of 5-FU [ Time Frame: Pre- infusion (0 hr) on Day 1 Cycle 1; end of 5-FU bolus and 2 and 12-24 hrs after end of 5-FU bolus (infusion duration = 46 hrs) on Day 1 of Cycles 1 and 3 (each cycle=14 days) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum Plasma Concentration of Oxaliplatin [ Time Frame: Pre-infusion (0 hr) on Day 1 Cycle 1; 5-10 min before end of oxaliplatin infusion (infusion duration = 120 min) and 2 and 12-24 hrs after end of 5-FU bolus (infusion duration = 46 hrs) on Day 1 of Cycles 1 and 3 (each cycle=14 days) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum Plasma Concentration of Carboplatin [ Time Frame: Pre-infusion (0 hr), 5-10 min before and 1 hr after carboplatin EOI (infusion duration=15-30 min),24 hr after atezolizumab EOI (infusion duration=90 min)on Day 1 Cycle 1; 5-10 min before and 1 hr after carboplatin EOI Day 1 Cycle 3 (each cycle=21 days) ] [ Designated as safety issue: No ]
  • Maximum Plasma Concentration of Paclitaxel [ Time Frame: Pre-infusion (0 hr), 5-10 min before and 1 hr after paclitaxel EOI (infusion duration=180 min), 24 hr after atezolizumab EOI (infusion duration=90 min) on Day 1 Cycle 1; 5-10 min before and 1 hr after paclitaxel EOI on Day 1 Cycle 3 (each cycle=21 days) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum Plasma Concentration of Pemetrexed [ Time Frame: Pre-infusion (0 hr), 5-10 min before and 1 hr after pemetrexed EOI (infusion duration=10 min), 24 hr after atezolizumab EOI (infusion duration=90 min) on Day 1 Cycle 1; 5-10 min before and 1 hr after pemetrexed EOI on Day 1 Cycle 3 (each cycle = 21 days) ] [ Designated as safety issue: No ]
  • Maximum Plasma Concentration of Nab-Paclitaxel (Total Paclitaxel) [ Time Frame: Pre-infusion (0 hr), 5-10 min before and 1 hr after nab-paclitaxel EOI (infusion duration=30 min) on Day 1 of Cycles 1 and 3; 24 hr after atezolizumab EOI (infusion duration=90 min) on Day 1 Cycle 1 (each cycle=7 days) ] [ Designated as safety issue: No ]
  • Number of Cycles of Each Component of Treatment Administer [ Time Frame: From Baseline up to approximately 5 years ] [ Designated as safety issue: No ]
  • Dose Intensity of Each Component of Treatment Administer [ Time Frame: From Baseline up to approximately 5 years ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Area under the concentration-time curve [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Best overall response (tumor assessments according to RECIST criteria) [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Objective response rate (complete response + partial response) [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Duration of objective response [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of Atezolizumab Administered in Combination With Bevacizumab and/or With Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors
Not Provided
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-programmed death-ligand 1 [PDL1] antibody) administered with bevacizumab (Arm A) and with bevacizumab plus oxaliplatin, leucovorin, and 5-fluorouracil (5-FU) (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.
Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Cancer
  • 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 mg/kg or 15 mg/kg IV q3w.
    Other Name: Avastin
  • Drug: Carboplatin
    Participants will receive carboplatin IV q3w with target AUC of 6 mg/mL.
  • Drug: Leucovorin
    Participants will receive leucovorin 400 mg/m^2 IV q2w.
  • Drug: Nab-paclitaxel
    Participants will receive nab-paclitaxel 100 mg/m^2 IV qw.
  • Drug: Oxaliplatin
    Participants will receive oxaliplatin 85 mg/m^2 IV q2w.
  • Drug: Paclitaxel
    Participants will receive paclitaxel 200 mg/m^2 IV q3w.
  • Drug: Pemetrexed
    Participants will receive pemetrexed 500 mg/m^2 IV q3w.
  • Experimental: A: Atezolizumab + Bevacizumab
    Participants will receive atezolizumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion (or a selected dose level not to exceed the single agent MTD or MAD determined in Study PCD4989g) with bevacizumab 15 mg/kg every 3 weeks (q3w). After establishment of MTD or MAD, participants will receive bevacizumab 15 mg/kg IV infusion on Day 1 of Cycle 1 followed by atezolizumab 1200 mg IV infusion q3w after Days 5-7 and then atezolizumab 1200 mg q3w and bevacizumab 15 mg/kg q3w on Day 1 of all subsequent cycles until disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Bevacizumab
  • Experimental: B: Atezolizumab + Bevacizumab + FOLFOX
    Participants will receive FOLFOX IV infusion (oxaliplatin [85 milligrams per square meter {mg/m^2}], leucovorin [400 mg/m^2], 5-FU [400 mg/m^2]) on Day 1 of Cycle 1 and then atezolizumab 800 mg IV infusion every 2 weeks (q2w), bevacizumab 10 mg/kg IV infusion q3w and FOLFOX q2w on Day 1 of all subsequent cycles as per institutional guidelines until disease progression or unacceptable toxicity.
    Interventions:
    • Drug: 5-FU
    • Drug: Atezolizumab
    • Drug: Bevacizumab
    • Drug: Leucovorin
    • Drug: Oxaliplatin
  • Experimental: C: Atezolizumab + Carboplatin + Paclitaxel
    Participants will receive atezolizumab 1200 mg IV infusion q3w in combination with paclitaxel 200 mg/m^2 IV infusion q3w and then carboplatin IV q3w (on Day 1 of every 3-week cycle) to achieve an initial target area under the curve (AUC) of 6 milligrams per milliliter*minute (mg/mL*min) until disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Carboplatin
    • Drug: Paclitaxel
  • Experimental: D: Atezolizumab + Carboplatin + Pemetrexed
    Participants will receive atezolizumab 1200 mg IV infusion q3w in combination with premetrexed 500 mg/m^2 IV infusion q3w and then carboplatin IV q3w (on Day 1 of every 3-week cycle) to achieve an initial target AUC of 6 mg/mL*min until disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Carboplatin
    • Drug: Pemetrexed
  • Experimental: E: Atezolizumab + Carboplatin + Nab-paclitaxel
    Participants will receive atezolizumab 1200 mg IV infusion q3w (on Day 1 of every 3-week cycle) in combination with nab-paclitaxel 100 mg/m^2 IV infusion once weekly (qw) (on Days 1, 8 and 15 of every 3-week cycle) and then carboplatin IV infusion q3w (on Day 1 of every 3-week cycle) to achieve an initial target AUC of 6 mg/mL*min until disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Carboplatin
    • Drug: Nab-paclitaxel
  • Experimental: F: Atezolizumab + Nab-paclitaxel
    Participants will receive atezolizumab 800 mg IV infusion q2w (Days 1 and 15) in combination with nab-paclitaxel 125 mg/m^2 IV infusion qw (on Days 1, 8 and 15 of every 3-week cycle) until disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Nab-paclitaxel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
235
December 2018
December 2018   (final data collection date for primary outcome measure)

Inclusion Criteria:

General Inclusion Criteria:

  • Histologically or cytologically documented advanced solid tumors
  • Adequate hematologic and end organ function
  • Measurable disease by RECIST v1.1
  • 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 and Arms A and 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 participant is eligible Arm A and B Safety Expansion Cohorts, Arm B Escalation Cohorts, and Arm B Biopsy Cohort (Liver Lesions)
  • Histologically or cytologically confirmed metastatic colorectal cancer (mCRC). Participants in the Arm A Safety Expansion Cohort must have mCRC for which established therapies have proved ineffective or intolerable. Participants with malignancies other than 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 renal cell carcinoma (RCC) Cohort:

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

Arm A Tumor Type-Specific Cohort:

Gastric Cancer:

- 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 participants with a specified tumor PD-L1 status (e.g., immunohistochemistry [IHC] status 0/1 or 2/3)

Ovarian Cancer:

- Measurable/assessable ovarian cancer (defined as epithelial ovarian, fallopian tube, or primary peritoneal cancer) that has progressed less than (<) 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

Bladder Cancer:

  • Histologically or cytologically documented locally advanced (T4b, any N; or any T, N 2-3) or metastatic (M1, Stage IV) transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra)
  • Participants with mixed histologies are required to have a dominant transitional cell pattern
  • Locally advanced bladder cancer must be inoperable based on involvement of pelvic sidewall or adjacent viscera (clinical stage T4b) or bulky nodal metastasis (N2-N3)
  • Disease progression during or following treatment with at least one platinum-containing regimen (e.g., GC, MVAC, CarboGem, etc.) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence

Cervical Cancer:

  • Persistent or recurrent squamous cell carcinoma of the cervix (including adenosquamous tumors)

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 estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor (HER)-negative (triple-negative) adenocarcinoma of the breast that has been treated with systemic cytotoxic therapy. Locally recurrent disease must not be amenable to resection with curative intent
  • Participants 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 participants with CRC and high microsatellite instability (MSI-H) may be enrolled

Exclusion Criteria:

General Exclusions

  • 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 any component of the atezolizumab formulation
  • History of autoimmune disease, idiopathic pulmonary fibrosis, human immunodeficiency virus (HIV), hepatitis B or 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
  • Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
  • History of myocardial infarction, unstable angina stroke or transient ischemic attack within 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 Bevacizumab-Specific Exclusions (Arms A and B) 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

Arm A Tumor Type-Specific Cohort:

Gastric Cancer:

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

Ovarian Cancer:

  • Refractory disease
  • History of bowel obstruction
  • >2 prior anticancer regimens
  • Prior approved or experimental anti-VEGF/VEGFR therapy (including, for example, bevacizumab or nintedanib)

Cervical Cancer:

- > 2 prior cytotoxic regimens, not including prior cisplatin-based chemotherapy concomitantly administered with primary pelvic radiation

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 participant for 5-FU toxicity

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

  • Prior chemotherapy for locally advanced or metastatic NSCLC
  • For participants 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
  • Participants 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
  • Participants 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
All
18 Years and older   (Adult, Senior)
No
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
United States
 
NCT01633970
GP28328, 2012-001422-10
Not Provided
Not Provided
Not Provided
Genentech, Inc.
Genentech, Inc.
Not Provided
Study Director: Clinical Trials Genentech, Inc.
Genentech, Inc.
November 2016

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