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A Phase 2 Study of MPDL3280A (an Engineered Anti-PDL1 Antibody) as Monotherapy or in Combination With Avastin (Bevacizumab) Compared to Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01984242
First received: November 7, 2013
Last updated: November 17, 2014
Last verified: November 2014
  Purpose

This multicenter, randomized, open-label study will evaluate the efficacy and sa fety of MPDL3280A as monotherapy or in combination with Avastin (bevacizumab) ve rsus sunitinib in patients with previously untreated locally advanced or metasta tic renal cell carcinoma. Patients in Arm A will receive MPDL3280A 1200 mg IV ev ery 3 weeks (6-week cycles) plus Avastin 15 mg/kg IV until disease progression. Patients in Arm B will receive MPDL3280A 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, patie nts in Arms B and C will be given the option to receive combination treatment wi th MPDL3280A and Avastin. Patients enrolled into arm B (MPDL3280A alone) in Eu rope (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 MPDL3280A and bevacizumab following disease progressi on, per local regulatory requirement.


Condition Intervention Phase
Renal Cell Carcinoma
Drug: bevacizumab [Avastin]
Drug: MPDL3280A
Drug: sunitinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE II, RANDOMIZED STUDY OF MPDL3280A 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: approximately 2.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival using investigator assessment per immune-related criteria [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
  • Overall response rate (complete + partial response) [ Time Frame: approximately 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: approximately 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 MPDL3280A + Avastin treatment [ Time Frame: approximately 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 MPDL3280A + 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 MPDL3280A + Avastin treatment [ Time Frame: approximately 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 MPDL3280A alone and in combination with bevacizumab: Area under the concentration-time curve [ Time Frame: Cycle 1 ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: January 2014
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: MPDL3280A + Avastin Drug: bevacizumab [Avastin]
15 mg/kg IV q3w (dosed in 6-week cycles), until disease progression
Drug: MPDL3280A
1200 mg IV q3w dosed in 6-week cycles until disease progression
Experimental: B: MPDL3280A; following PD: MPDL3280A + Avastin Drug: bevacizumab [Avastin]
Following disease progression: 15 mg/kg IV q3w (dosed in 6-week cycles), until disease progression
Drug: MPDL3280A
1200 mg IV q3w dosed in 6-week cycles until disease progression
Drug: MPDL3280A
Following disease progression: 1200 mg IV q3w dosed in 6-week cycles, until disease progression
Active Comparator: C: Sunitinib; following PD: MPDL3280A + Avastin Drug: bevacizumab [Avastin]
Following disease progression: 15 mg/kg IV q3w (dosed in 6-week cycles), until disease progression
Drug: MPDL3280A
Following disease progression: 1200 mg 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
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 MPDL3280A or Avastin, or at least 30 days after the last dose of sunitinib

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

Contacts
Contact: Reference Study ID Number: WO29074 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

  Hide Study Locations
Locations
United States, Arizona
Recruiting
Scottsdale, Arizona, United States, 85258
United States, California
Recruiting
Duarte, California, United States, 91010
Recruiting
Los Angeles, California, United States, 90024
Recruiting
San Francisco, California, United States, 94143
United States, Colorado
Recruiting
Aurora, Colorado, United States, 80045
Recruiting
Denver, Colorado, United States, 80218
United States, Connecticut
Recruiting
New Haven, Connecticut, United States, 06510-3289
United States, District of Columbia
Recruiting
Washington, District of Columbia, United States, 20016-1468
United States, Florida
Recruiting
Ft Myers, Florida, United States, 33916
Recruiting
Jacksonville, Florida, United States, 32224
Recruiting
St Petersburg, Florida, United States, 33705
United States, Illinois
Not yet recruiting
Chicago, Illinois, United States, 60611
Recruiting
Chicago, Illinois, United States, 60637
United States, Maryland
Not yet recruiting
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Not yet recruiting
Boston, Massachusetts, United States, 02115
Not yet recruiting
Boston, Massachusetts, United States, 02215
Recruiting
Boston, Massachusetts, United States, 02114
United States, Michigan
Recruiting
Detroit, Michigan, United States, 48201
United States, Nevada
Recruiting
Las Vegas, Nevada, United States, 89148
United States, New York
Recruiting
New York, New York, United States
United States, Ohio
Recruiting
Cincinnati, Ohio, United States, 45242
Recruiting
Cleveland, Ohio, United States, 44195
United States, Oregon
Recruiting
Eugene, Oregon, United States, 97401
Recruiting
Tualatin, Oregon, United States, 97062
United States, South Carolina
Completed
Columbia, South Carolina, United States, 10595
United States, Tennessee
Recruiting
Nashville, Tennessee, United States, 37232-7610
Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Recruiting
Dallas, Texas, United States, 75246
Czech Republic
Not yet recruiting
Hradec Kralove, Czech Republic, 50005
Not yet recruiting
Labem, Czech Republic, 40113
Not yet recruiting
Olomouc, Czech Republic, 775 20
Not yet recruiting
Prague, Czech Republic, 15060
France
Recruiting
Angers, France, 49933
Recruiting
Lille, France, 59020
Recruiting
Lyon, France, 69373
Recruiting
Paris, France, 75908
Recruiting
Paris, France, 75475
Recruiting
Pessac, France, 33604
Recruiting
Toulouse, France, 31059
Recruiting
Villejuif, France, 94805
Germany
Not yet recruiting
Essen, Germany, 45122
Not yet recruiting
Hannover, Germany, 30625
Not yet recruiting
Munich, Germany, 81675
Not yet recruiting
München, Germany, 81377
Italy
Not yet recruiting
Meldola, Emilia-Romagna, Italy, 47014
Not yet recruiting
Modena, Emilia-Romagna, Italy, 41124
Not yet recruiting
Cremona, Lombardia, Italy, 26100
Recruiting
Milano, Lombardia, Italy, 20133
Not yet recruiting
Milano, Lombardia, Italy, 20132
Not yet recruiting
Pavia, Lombardia, Italy, 27100
Recruiting
Arezzo, Toscana, Italy, 52100
Not yet recruiting
Siena, Toscana, Italy, 53100
Poland
Not yet recruiting
Gdansk, Poland, 80-214
Not yet recruiting
Lublin, Poland, 20-090
Not yet recruiting
Poznan, Poland, 60-569
Not yet recruiting
Warszawa, Poland, 04-125
Romania
Not yet recruiting
Brasov, Romania, 500091
Not yet recruiting
Cluj Napoca, Romania, 400015
Not yet recruiting
Cluj-Napoca, Romania, 400058
Not yet recruiting
Sata Mare, Romania, 440055
Spain
Recruiting
Barcelona, Spain, 08036
Recruiting
Barcelona, Spain, 08035
Recruiting
Madrid, Spain, 28041
Recruiting
Madrid, Spain, 28050
Recruiting
Zaragoza, Spain, 50009
United Kingdom
Recruiting
Bebington, United Kingdom, CH63 4JY
Recruiting
London, United Kingdom, EC1A 7BE
Recruiting
London, United Kingdom, SW3 6JJ
Recruiting
Manchester, United Kingdom, M2O 4BX
Not yet recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

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: November 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Bevacizumab
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014