A Phase 2 Study of Atezolizumab (an Engineered Anti-PDL1 Antibody) as Monotherapy or in Combination With Avastin (Bevacizumab) Compared to Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma [IMmotion150]

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01984242
First received: November 7, 2013
Last updated: July 1, 2016
Last verified: July 2016
  Purpose

This multicenter, randomized, open-label study will evaluate the efficacy and safety of atezolizumab as monotherapy or in combination with Avastin (bevacizumab) versus sunitinib in patients with previously untreated locally advanced or metastatic renal cell carcinoma. Patients in Arm A will receive atezolizumab 1200 mg IV every 3 weeks (6-week cycles) plus Avastin 15 mg/kg IV until disease progression. Patients in Arm B will receive atezolizumab alone (until disease progression), and patients in Arm C will receive sunitinib 50 mg orally daily for 4 weeks followed by 2 weeks rest until disease progression. Following disease progression, patients in Arms B and C will be given the option to receive combination treatment with atezolizumab and Avastin.

Patients enrolled into arm B (atezolizumab alone) in Europe (including France, Italy, the United Kingdom, Romania, Spain, Germany, the Czech Republic and Poland) are not eligible to cross over into arm A to receive combination treatment with atezolizumab and bevacizumab following disease progression, per local regulatory requirement.


Condition Intervention Phase
Renal Cell Carcinoma
Drug: atezolizumab
Drug: bevacizumab [Avastin]
Drug: sunitinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Randomized Study of Atezolizumab Administered as Monotherapy or In Combination With Bevacizumab Versus Sunitinib In Patients With Untreated Advanced Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-free survival per RECIST v.1.1 via central IRC assessment [ Time Frame: Up to 2.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival using investigator assessment per immune-related criteria [ Time Frame: Up to 2.5 years ] [ Designated as safety issue: No ]
  • Overall response rate (complete + partial response) [ Time Frame: Up to 2.5 years ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 2.5 years ] [ Designated as safety issue: No ]
  • Overall response rate in patients progressing on the sunitinib and MPDL alone arms who subsequently cross over to atezolizumab + Avastin treatment [ Time Frame: Up to 1.5 years ] [ Designated as safety issue: No ]
  • Duration of response in patients progressing on the sunitinib and MPDL alone arms who subsequently cross over to atezolizumab + Avastin treatment [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
  • Progression-free survival in patients progressing on the sunitinib and MPDL alone arms who subsequently cross over to atezolizumab + Avastin treatment [ Time Frame: Up to 1.5 years ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
  • Pharmacokinetics of atezolizumab alone and in combination with bevacizumab: Area under the concentration-time curve [ Time Frame: Cycle 1 ] [ Designated as safety issue: No ]

Enrollment: 305
Study Start Date: January 2014
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: atezolizumab + Avastin Drug: atezolizumab
1200 mg IV q3w dosed in 6-week cycles until disease progression
Drug: bevacizumab [Avastin]
15 mg/kg IV q3w (dosed in 6-week cycles), until disease progression
Experimental: B: atezolizumab; following PD: atezolizumab + Avastin Drug: atezolizumab
1200 mg IV q3w dosed in 6-week cycles until disease progression
Drug: atezolizumab
Following disease progression: 1200 mg IV q3w dosed in 6-week cycles, until disease progression
Drug: bevacizumab [Avastin]
Following disease progression: 15 mg/kg IV q3w (dosed in 6-week cycles), until disease progression
Active Comparator: C: Sunitinib; following PD: atezolizumab + Avastin Drug: atezolizumab
Following disease progression: 1200 mg IV q3w dosed in 6-week cycles, until disease progression
Drug: bevacizumab [Avastin]
Following disease progression: 15 mg/kg IV q3w (dosed in 6-week cycles), until disease progression
Drug: sunitinib
50 mg/day orally for 4 weeks, followed by 2 weeks of rest (dosed on 6-week cycles), until disease progression

  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 >/= 18 years of age
  • Unresectable advanced or metastatic renal cell carcinoma with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic agents, including treatment in the adjuvant setting
  • Measurable disease, as defined by RECIST v1.1
  • Karnofsky performance score >/= 70
  • Adequate hematologic and end-organ function as defined by protocol
  • Women of childbearing potential and male patients must agree to use adequate methods of contraception as defined by protocol during the treatment period and for at least 6 months after the last dose of atezolizumab or Avastin (bevacizumab) for patients randomized to Arm A, or at least 90 days after the last dose of atezolizumab monotherapy for patients randomized to Arm B, or at least 30 days after the last dose of sunitinib for patients randomized to Arm C.

Exclusion Criteria:

  • Radiotherapy for RCC within 28 days prior to Cycle 1, Day 1 with the exception of: Single-fraction radiotherapy given for the indication of pain control
  • Known active malignancies or metastasis of the brain or spinal cord or leptomeningeal disease, as determined by CT or MRI evaluation during screening and prior radiographic assessments
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
  • Uncontrolled hypercalcemia or symptomatic hypercalcemia
  • Malignancies other than RCC within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death, treated with expected curative outcome
  • Life expectancy of < 12 weeks
  • Pregnant and lactating women
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • History of autoimmune disease (Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study)

Bevacizumab- and Sunitinib-Specific Exclusions:

  • Inadequately controlled hypertension
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  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: NCT01984242

  Hide Study Locations
Locations
United States, Arizona
Scottsdale, Arizona, United States, 85258
United States, California
Duarte, California, United States, 91010
Los Angeles, California, United States, 90024
San Francisco, California, United States, 94143
United States, Colorado
Aurora, Colorado, United States, 80045
Denver, Colorado, United States, 80218
United States, Connecticut
New Haven, Connecticut, United States, 06510-3289
United States, District of Columbia
Washington, District of Columbia, United States, 20016-1468
United States, Florida
Ft Myers, Florida, United States, 33916
Jacksonville, Florida, United States, 32224
St Petersburg, Florida, United States, 33705
United States, Illinois
Chicago, Illinois, United States, 60637
United States, Massachusetts
Boston, Massachusetts, United States, 02215
Boston, Massachusetts, United States, 02115
Boston, Massachusetts, United States, 02114
United States, Michigan
Detroit, Michigan, United States, 48201
United States, Nevada
Las Vegas, Nevada, United States, 89148
United States, New York
New York, New York, United States
United States, Ohio
Cincinnati, Ohio, United States, 45242
Cleveland, Ohio, United States, 44195
United States, Oregon
Eugene, Oregon, United States, 97401
Tualatin, Oregon, United States, 97062
United States, South Carolina
Columbia, South Carolina, United States, 10595
United States, Tennessee
Nashville, Tennessee, United States, 37203
Nashville, Tennessee, United States, 37232-7610
United States, Texas
Dallas, Texas, United States, 75246
Czech Republic
Olomouc, Czech Republic, 775 20
Praha 5, Czech Republic, 150 06
Ústí nad Labem, Czech Republic, 401 13
France
Angers, France, 49055
Lille, France, 59020
Lyon, France, 69373
Paris, France, 75475
Paris, France, 75908
Pessac, France, 33604
Toulouse, France, 31059
Villejuif, France, 94805
Germany
Hannover, Germany, 30625
Munich, Germany, 81675
München, Germany, 81377
Italy
Milano, Lombardia, Italy, 20133
Milano, Lombardia, Italy, 20132
Arezzo, Toscana, Italy, 52100
Siena, Toscana, Italy, 53100
Poland
Warszawa, Poland, 04-125
Romania
Cluj Napoca, Romania, 400015
Cluj-Napoca, Romania, 400058
Satu Mare, Romania, 440055
Spain
Pamplona, Navarra, Spain, 31008
Barcelona, Spain, 08035
Barcelona, Spain, 08036
Madrid, Spain, 28041
Madrid, Spain, 28050
Zaragoza, Spain, 50009
United Kingdom
Bebington, United Kingdom, CH63 4JY
London, United Kingdom, EC1A 7BE
London, United Kingdom, SW3 6JJ
Manchester, United Kingdom, M2O 4BX
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01984242     History of Changes
Other Study ID Numbers: WO29074  2013-003167-58 
Study First Received: November 7, 2013
Last Updated: July 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Polystyrene sulfonic acid
Bevacizumab
Sunitinib
Antibodies, Monoclonal
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 28, 2016