This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback
Trial record 1 of 2 for:    29322
Previous Study | Return to List | Next Study

A Study to Assess the Safety and Tolerability of Atezolizumab in Combination With Other Immune-Modulating Therapies in Participants With Locally Advanced or Metastatic Solid Tumors

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02174172
First received: June 19, 2014
Last updated: May 26, 2017
Last verified: May 2017
  Purpose
This global, multicenter, open-label study will evaluate the safety and tolerability of atezolizumab in combination with other immune-modulating therapies in the treatment of selected advanced or metastatic malignancies. The atezolizumab plus ipilimumab arm (Arm A) will focus primarily on participants with advanced or metastatic non-small cell lung cancer (NSCLC). The atezolizumab plus interferon alfa-2b arm (Arm B), plus pegylated interferon alfa-2a (PEG−interferon alfa-2a, Arm C), and atezolizumab plus PEG-interferon Alfa-2a plus bevacizumab (Arm D) will enroll participants with advanced or metastatic renal cell carcinoma (RCC), metastatic NSCLC and melanoma. The atezolizumab plus obinutuzumab) (Arm E) will enroll participants with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Atezolizumab will be administered as intravenous (IV) infusion every 3 weeks (q3w).

Condition Intervention Phase
Solid Cancers Drug: Atezolizumab Drug: Bevacizumab Drug: Interferon alfa-2b Drug: Ipilimumab Drug: Obinutuzumab Drug: PEG-interferon alfa-2a Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase Ib Study of The Safety And Pharmacology of Atezolizumab (Anti−Pd-L1 Antibody) Administered With Ipilimumab, Interferon-Alpha, or Other Immune-Modulating Therapies in Patients With Locally Advanced or Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Recommended Phase II Dose (RP2D) of Atezolizumab When Given in Combination With Ipilimumab and Interferon Alfa-2b [ Time Frame: From the first atezolizumab treatment up to 21 days ]
  • Percentage of Participants with Advere Events [ Time Frame: From the first atezolizumab treatment up to 4.5 years (yr) ]

Secondary Outcome Measures:
  • Percentage of Participants with Best Overall Response, as Assessed Using Conventional Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]) ]
  • Percentage of Participants with Best Overall Response, as Assessed Using Immune Modified RECIST Criteria [ Time Frame: Screening to progression or death, up to 4.5 years (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]) ]
  • Duration of Objective Response [ Time Frame: Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]) ]
  • Overall Survival [ Time Frame: Baseline to death (up to 4.5 yr) ]
  • Progression-Free Survival [ Time Frame: Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]) ]
  • Percentage of Participants with Objective Response, as Assessed Using Conventional RECIST v1.1 [ Time Frame: Screening to progression or death, up to 4.5 yr (assessed at Baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]) ]
  • Percentage of Participants with Objective Response, as Assessed Using Immune Modified RECIST Criteria [ Time Frame: Screening to progression or death, up to 4.5 yr (assessed at Baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr]) ]
  • Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Baseline up to 4.5 years (detailed timeframe is given in outcome description) ]

    Arm A: Predose (0 hour [hr]), 30 minutes (min) post end of infusion on Day 1;Day 8,Day 15 of Cycle (cy) 1;Predose (0 hr) on Day 1 of cy 2,3,4,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 years [yr]). Arm B: Predose (0 hr) on Day 1,30 min post end of infusion on Day 8,Day 15,Day 22 of cy 1;Predose (0 hr) on Day 1 of cy 2,3,4,5,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Arms C,D: Predose (0 hr), 30 min post end of infusion on Day 1 cy 1,3;Predose (0 hr) on Day 1 of cy 2,4,8, every 8 cy thereafter up to end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Arm E: Predose (0 hr), 30 min post end of infusion on Day 1 cy 1,5;Predose (0 hr) on Day 1 of cy 2,3,4,8, every 8 cy thereafter up to treatment end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Cycle length: Arms A,C,D,E: 21 days; Arm B: 28 days for cy 1, 21 days for other cy.

    Infusion duration: 1 hr for first infusion, 30 min for subsequent infusions


  • Minimum Serum Concentration of Atezolizumab [ Time Frame: Baseline up to 4.5 years (detailed timeframe is given in outcome description) ]

    Arm A: Predose (0 hour [hr]), 30 minutes (min) post end of infusion on Day 1;Day 8,Day 15 of Cycle (cy) 1;Predose (0 hr) on Day 1 of cy 2,3,4,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 years [yr]). Arm B: Predose (0 hr) on Day 1,30 min post end of infusion on Day 8,Day 15,Day 22 of cy 1;Predose (0 hr) on Day 1 of cy 2,3,4,5,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Arms C,D: Predose (0 hr), 30 min post end of infusion on Day 1 cy 1,3;Predose (0 hr) on Day 1 of cy 2,4,8, every 8 cy thereafter up to end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Arm E: Predose (0 hr), 30 min post end of infusion on Day 1 cy 1,5;Predose (0 hr) on Day 1 of cy 2,3,4,8, every 8 cy thereafter up to treatment end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Cycle length: Arms A,C,D,E: 21 days; Arm B: 28 days for cy 1, 21 days for other cy.

    Infusion duration: 1 hr for first infusion, 30 min for subsequent infusions


  • Cmax of Ipilimumab [ Time Frame: Predose (0 hr), 30 min post end of infusion on Day 1 of Cy 1,3;Predose on Day 1 of Cy 4; end of treatment/ withdrawal;≥ 90 days post last dose (up to 4.5 yr); Cy length: 21 days; Duration of infusion: 90 min ]
  • Cmax of Bevacizumab [ Time Frame: Predose (0 hr), 30 min post end of infusion on Day 1 of Cy 1,3; end of treatment/ withdrawal;≥ 90 days post last dose (up to 4.5 yr); Cy length: 21 days; Duration of infusion: 90 min for 1st infusion, 30-60 min for all other infusions ]
  • Cmax of Obinutuzumab [ Time Frame: Predose (0 hr), 30 min post end of infusion on Days -13, -12 and on Day 1 Cy 5; end of treatment/withdrawal;≥90 days post last dose (up to 4.5 yr); Cy length: 21 days; Duration of infusion: approximately 4.5 hr for 1st infusion,3.5 hr for other infusions ]
  • Anti-Therapeutic Antibody to Atezolizumab [ Time Frame: Baseline up to 4.5 years (detailed timeframe is given in outcome description) ]

    Detailed timeframe:

    Arm A: Predose (0 hr) on Day 1 of Cy 1,2,3,4,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr).

    Arm B: Predose (0 hr) on Day 1 of Cy 1,2,3,4,5,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr).

    Arms C, D, E: Predose (0 hr) on Day 1 of cy 1,2,3,4,5,8, thereafter every 8 Cyup to end of treatment/ withdrawal;≥ 90 days post last dose (up to 4.5 yr). Cy length: Arms A,C,D,E: 21 days; Arm B: 28 days for Cy 1, 21 days for other Cy.

    Infusion duration: 1 hr for first infusion, 30 min for subsequent infusions.


  • Anti-Therapeutic Antibody to Ipilimumab [ Time Frame: Pre-dose (0 hr) on Day 1 of Cy 1, 4, end of treatment/ withdrawal;≥ 90 days post last dose (up to 4.5 yr); Cy length:21 days. Duration of infusion: Duration of infusion: 90 min ]
  • Anti-Therapeutic Antibody to Bevacizumab [ Time Frame: Predose (0 hr) on Day 1 of Cy 1, 3; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Cy length: 21 days. Duration of infusion: 90 min for 1st infusion, 30-60 min for all other infusions ]
  • Anti-Therapeutic Antibody to Obinutuzumab [ Time Frame: Predose (0 hr) on Days -13 and -12; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr) ]

Estimated Enrollment: 200
Actual Study Start Date: August 18, 2014
Estimated Study Completion Date: February 28, 2019
Estimated Primary Completion Date: February 28, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Atezolizumab with Ipilimumab
Participants will receive atezolizumab along with ipilimumab.
Drug: Atezolizumab
Participant will receive atezolizumab 600 milligrams (mg) or 1200 mg by IV infusion q3w.
Other Name: Tecentriq, RO5541267, MPDL3280A
Drug: Ipilimumab
Participants will receive Ipilimumab 1, or 3 mg/kg IV, single dose, or multiple-dose regimen q3w for up to 4 cycles.
Experimental: Arm B: Atezolizumab with Interferon alfa-2b
Participants will receive atezolizumab along with Interferon alfa-2b.
Drug: Atezolizumab
Participant will receive atezolizumab 600 milligrams (mg) or 1200 mg by IV infusion q3w.
Other Name: Tecentriq, RO5541267, MPDL3280A
Drug: Interferon alfa-2b
Participants will receive Interferon alfa-2b 3, 5, or 10 million international units subcutaneously every other day for up to 3 doses per week.
Experimental: Arm C: Atezolizumab with PEG- interferon alfa-2a
Participants will receive atezolizumab along with PEG- interferon alfa-2a.
Drug: Atezolizumab
Participant will receive atezolizumab 600 milligrams (mg) or 1200 mg by IV infusion q3w.
Other Name: Tecentriq, RO5541267, MPDL3280A
Drug: PEG-interferon alfa-2a
Participant will receive PEG-interferon alfa-2a 180 micrograms subcutaneous injection q3w for a total of 6 cycles.
Other Name: Pegasys®
Experimental: Arm D:Atezolizumab with PEG-interferon alfa-2a and Bevacizumab
Participants will receive atezolizumab along with PEG- interferon alfa-2a and bevacizumab.
Drug: Atezolizumab
Participant will receive atezolizumab 600 milligrams (mg) or 1200 mg by IV infusion q3w.
Other Name: Tecentriq, RO5541267, MPDL3280A
Drug: Bevacizumab
Participant will receive Bevacizumab 15 milligrams per kilograms (mg/kg) IV infusion q3w.
Other Name: Avastin®
Drug: PEG-interferon alfa-2a
Participant will receive PEG-interferon alfa-2a 180 micrograms subcutaneous injection q3w for a total of 6 cycles.
Other Name: Pegasys®
Experimental: Arm E: Atezolizumab with Obinutuzumab
Participants will receive atezolizumab along with obinutuzumab or atezolizumab alone.
Drug: Atezolizumab
Participant will receive atezolizumab 600 milligrams (mg) or 1200 mg by IV infusion q3w.
Other Name: Tecentriq, RO5541267, MPDL3280A
Drug: Obinutuzumab
Obinutuzumab 1000 milligrams will be administered as pre-treatment on 2 consecutive days (Day -13 and Day -12) prior to treatment start with atezolizumab on Cycle 1, Day 1 (cycle length=21 days). An additional two doses of obinutuzumab will be administered on Days 85 and 86 of study treatment (Cycle 5, Day 1 and Cycle 5, Day 2).

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically documented locally advanced or metastatic solid tumors meeting the following study drug-specific criteria:
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • Life expectancy greater than or equal to (>/=) 12 weeks
  • Measurable disease, as defined by RECIST v1.1
  • Adequate hematologic and end organ function as confirmed by laboratory results within 14 days prior to the first study treatment

Inclusion criteria specific to Arm A: Atezolizumab+ Ipilimumab

  • Escalation stage: NSCLC participants
  • Mandatory biopsy cohort: NSCLC or melanoma atezolizumab
  • Prior atezolizumab-treated cohort: participants with NSCLC or melanoma previously treated with atezolizumab

Inclusion criteria specific to Arm B: Atezolizumab+ Interferon alfa-2b

  • Escalation stage: RCC or melanoma participants
  • Expansion stage: RCC or melanoma participants
  • Mandatory biopsy cohort: RCC or melanoma participants
  • Prior immunotherapy-treated cohort: participants with RCC, NSCLC, or melanoma previously treated with programmed death-ligand 1 (PD-L1)/ Programmed death 1 (PD-1)

Inclusion Criteria Specific to Arm C (Atezolizumab plus PEG-Interferon Alafa-2a):

  • Cohort 1: participants with RCC
  • Cohort 2: participants who were previously treated with anti-PD-L1/PD-1 with locally advanced or metastatic solid tumor (e.g., NSCLC, RCC, or melanoma)

Inclusion Criteria Specific to Arm D (Atezolizumab plus PEG−Interferon Alfa-2a +Bevacizumab)

  • Cohort 1: participants with metastatic RCC with no prior line of systemic therapy for metastatic disease
  • Cohorts 2-3: disease progression during or after at least one previous systemic, anti-cancer treatment for locally advanced or metastatic solid tumors; participants with sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements must have failed or are intolerant to prior treatment with EGFR or ALK inhibitors; participants with melanoma with actionable BRAF mutations (e.g., V600) must have failed or are intolerant to prior treatment with BRAF inhibitors

Inclusion Criteria Specific to Arm E (Atezolizumab +Obinutuzumab)

- R/M HNSCC participants with at least one prior line of systemic therapy

Inclusion Criteria Specific to prior Anti−PD-L1/PD-1 Treated Cohorts:

  • No permanent discontinuation of atezolizumab or other immunotherapies due to a treatment-related adverse event
  • Recovery from all immunotherapy-related adverse events to Grade less than or equal to (≤) 1 or baseline at the time of consent

Exclusion Criteria:

General Medical Exclusions:

  • Pregnant and lactating women
  • Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment, with the following exception: (1) hormone-replacement therapy or oral contraceptives; (2) tyrosine kinase inhibitors (TKIs) that have been discontinued greater than (>) 7 days prior to Cycle 1, Day 1, baseline scans must be obtained after discontinuation of prior TKIs
  • Investigational therapy within 28 days prior to initiation of study treatment
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of the atezolizumab formulation
  • History of or active autoimmune disease
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, risk of pulmonary toxicity, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • History of human immunodeficiency virus (HIV)
  • Participants with active hepatitis B
  • Participants with active hepatitis C
  • Participants with active tuberculosis
  • Participants with a history of confirmed progressive multifocal leukoencephalopathy
  • Any serious medical condition, physical examination finding, or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study

Cancer-Specific Exclusions:

  • Active or untreated central nervous system (CNS) metastases, as determined by CT or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
  • Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >/= 2 weeks prior to screening
  • Leptomeningeal disease
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently); participants with indwelling catheters are allowed.
  • Uncontrolled tumor-related pain
  • Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
  • History of other malignancy within 2 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, localized prostate cancer treated with curative intent, ductal carcinoma in situ treated surgically with curative intent, or other cancers with a similar outcome

Exclusion Criteria Related to Medications:

  • Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies (Note: Participants enrolled in the prior anti−PD-L1/PD-1 treated cohorts with melanoma may have received prior anti-cytotoxic T-lymphocyte-associated protein 4 treatment or other immunotherapies)
  • Treatment with systemic immunostimulatory agents within four weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
  • Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1 (the use of inhaled corticosteroids and mineralocorticoids is allowed)

Exclusion Criteria Specific to Interferon Alpha Therapy (Arms B−D):

  • History of depression, suicidal ideation or behavior, bipolar disorder, or psychosis
  • Hypersensitivity to interferon alpha or any component of the product

Exclusion Criteria Specific to Bevacizumab (Arm D)

  • Inadequately controlled hypertension
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • Significant vascular disease within 6 months prior to Day 1
  • History of hemoptysis
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • History of tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
  • Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
  • Evidence of abdominal free air that is not explained by paracentesis or recent surgical procedure
  • Proteinuria, as demonstrated by urine dipstick or > 1.0 gram of protein in a 24-hour urine collection
  • Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses of large volume

Exclusion Criteria Specific Obinutuzumab (Arm E)

  • Hypersensitivity to obinutuzumab
  • Prior treatment with obinutuzumab
  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: NCT02174172

Contacts
Contact: Reference Study ID Number: GO29322 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
United States, Arizona
HonorHealth Research Institute - Pima Center Recruiting
Scottsdale, Arizona, United States, 85258
Mayo Clinic- Scottsdale Recruiting
Scottsdale, Arizona, United States, 85259
United States, California
UCLA Recruiting
Los Angeles, California, United States, 90095
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06510
United States, Florida
Mayo Clinic-Jacksonville Completed
Jacksonville, Florida, United States, 32224
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
United States, Tennessee
Sarah Cannon Research Inst. Recruiting
Nashville, Tennessee, United States, 37203
Vanderbilt Medical Center Recruiting
Nashville, Tennessee, United States, 37232-7610
Netherlands
The Netherlands Cancer Insitute of Amsterdam Recruiting
Amsterdam, Netherlands, 1066 CX
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02174172     History of Changes
Other Study ID Numbers: GO29322
2014-000812-33 ( EudraCT Number )
Study First Received: June 19, 2014
Last Updated: May 26, 2017

Additional relevant MeSH terms:
Bevacizumab
Obinutuzumab
Interferons
Interferon-alpha
Peginterferon alfa-2a
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors

ClinicalTrials.gov processed this record on June 22, 2017