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 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: August 27, 2014
Last verified: August 2014
  Purpose

This multicenter, randomized, open-label study will evaluate the efficacy and safety of MPDL3280A 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 MPDL3280A 1200 mg IV every 3 weeks (eight 6-week cycles or up to 1 year) plus Avastin 15 mg/kg IV until disease progression. Patients in Arm B will receive MPDL3280A alone (up to 1 year), 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 MPDL3280A and Avastin.


Condition Intervention Phase
Renal Cell Carcinoma
Drug: MPDL3280A
Drug: bevacizumab [Avastin]
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 ICR 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: 150
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: MPDL3280A
1200 mg IV q3w (dosed in 6-week cycles), 8 cycles (or up to 1 year, whichever comes first)
Drug: bevacizumab [Avastin]
15 mg/kg IV q3w (dosed in 6-week cycles), until disease progression
Experimental: B: MPDL3280A; following PD: MPDL3280A + Avastin Drug: MPDL3280A
1200 mg IV q3w (dosed in 6-week cycles), 8 cycles (or up to 1 year, whichever comes first)
Drug: MPDL3280A
Following disease progression: 1200 mg IV q3w (dosed in 6-week cycles), 8 cycles (or up to 1 year, whichever comes first)
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: MPDL3280A + Avastin Drug: sunitinib
50 mg/day orally for 4 weeks, followed by 2 weeks of rest (dosed on 6-week cycles), until disease progression
Drug: MPDL3280A
Following disease progression: 1200 mg IV q3w (dosed in 6-week cycles), 8 cycles (or up to 1 year, whichever comes first)
Drug: bevacizumab [Avastin]
Following disease progression: 15 mg/kg IV q3w (dosed in 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 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 malignancies or metastasis of the brain or spinal cord or leptomeningeal disease
  • 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

  Show 71 Study Locations
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: August 27, 2014
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
Bevacizumab
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014