A Study of MPDL3280A in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02108652
First received: April 7, 2014
Last updated: September 22, 2014
Last verified: September 2014
  Purpose

This phase II, single-arm study was designed to evaluate the effect of MPDL3280A treatment in patients with locally advanced or metastatic urothelial bladder ca ncer. Patients will be enrolled into 1 of 2 cohorts. Cohort 1 will consist of pa tients who are treatment-naïve and ineligible for platinum-containing therapy. C ohort 2 will contain patients who have progressed during or following a prior pl atinum-based chemotherapy regimen. Patients in both cohorts will be given a 1200 mg intravenous (IV) dose of MPDL3280A on Day 1 of 21-day cycles. Treatment may continue for up to 16 cycles or 12 months, whichever is first, in the absence of toxicity or disease progression. Patients will be followed for up for 2 years. Patients who complete the initial treatment stage of up to 16 cycles may be eli gible for MPDL3280A re-treatment upon subsequent disease progression during the follow-up period and without intervening systemic anti-cancer therapy.


Condition Intervention Phase
Carcinoma, Transitional Cell , Bladder Cancer, Bladder Tumors, Urinary Bladder Neoplasms
Drug: MPDL3280A
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Single-Arm Study of MPDL3280A in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Objective response rate (ORR) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of response (DOR) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Incidence of adverse events [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Incidence of anti-therapeutic antibodies to MPDL3280A [ Time Frame: Up to 14 months ] [ Designated as safety issue: No ]
  • Maximum serum concentration (Cmax) of MPDL3280A [ Time Frame: Up to 14 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 330
Study Start Date: May 2014
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Treatment-naive and cisplatin-ineligible patients
Drug: MPDL3280A
1200 mg dose given by intravenous infusion (IV) on Day 1 of 21-day cycles for up to 16 cycles or 12 months (whichever comes first)
Experimental: Cohort 2
Patients with disease progression following or during platinum-containing treatment
Drug: MPDL3280A
1200 mg dose given by intravenous infusion (IV) on Day 1 of 21-day cycles for up to 16 cycles or 12 months (whichever comes first)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >/= 18 years
  • Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra)
  • Representative tumor specimens as specified by the protocol
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy >/= 12 weeks
  • Measurable disease, as defined by RECIST v1.1
  • Adequate hematologic and end organ function

Cohort 1-Specific Inclusion Criteria

  • Ineligible for cisplatin-based chemotherapy due to one of the following:
  • Impaired renal function
  • A hearing loss of 25 dB at two contiguous frequencies
  • Grade 2 or greater peripheral neuropathy
  • ECOG performance score of 2

Cohort 2-Specific Inclusion Criteria

  • Disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine and cisplatin [GC], methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC], CarboGem, etc.) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence

Exclusion Criteria:

  • Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
  • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
  • Active or untreated central nervous system (CNS) metastases as determined by CT or MRI evaluation during screening and prior radiographic assessments
  • Leptomeningeal disease
  • Malignancies other than UBC 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 or incidental prostate cancer
  • Pregnant and lactating women
  • History of autoimmune disease
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
  • Serum albumin < 2.5 g/dL
  • Positive test for HIV and/or active hepatitis B or hepatitis C or tuberculosis
  • Severe infections within 4 weeks prior to Cycle 1, Day 1
  • Significant cardiovascular disease
  • Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1
  • Prior allogeneic stem cell or solid organ transplant
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  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: NCT02108652

Contacts
Contact: Reference Study ID Number: GO29293 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

  Show 97 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: NCT02108652     History of Changes
Other Study ID Numbers: GO29293
Study First Received: April 7, 2014
Last Updated: September 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Hoffmann-La Roche:
anti-PD-L1
PD-L1
anti-PDL1
antiPD-L1
PDL1
MPDL3280A
PD-1
bladder cancer

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 01, 2014