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

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Jacksonville, Florida: 14-001529
    • Rochester, Minnesota: 14-001529
    NCT ID: NCT02108652
    Sponsor Protocol Number: GO29293

About this study

This phase II, single-arm study was designed to evaluate the effect of MPDL3280A treatment in patients with locally advanced or metastatic urothelial bladder cancer. Patients will be enrolled into 1 of 2 cohorts. Cohort 1 will consist of patients who are treatment-naïve and ineligible for platinum-containing therapy. Cohort 2 will contain patients who have progressed during or following a prior platinum-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 eligible for MPDL3280A re-treatment upon subsequent disease progression during the follow-up period and without intervening systemic anti-cancer therapy.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • 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 greater than or equal to (>=) 12 weeks
  • Measurable disease, as defined by RECIST v1.1
  • Adequate hematologic and end organ function

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.
  • A regimen was defined as participants receiving at least two cycles of a platinum-containing regimen. Participants who had received one cycle of a platinum-containing regimen but discontinued due to Grade 4 hematologic toxicity or Grade 3 or 4 non-hematologic toxicity could also be eligible.
  • Participants who received prior adjuvant/neoadjuvant chemotherapy and progressed within 12 months of treatment with a platinum-containing adjuvant/neoadjuvant regimen were considered as second-line participants.

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 computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
  • Leptomeningeal disease
  • Uncontrolled tumor-related pain
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
  • Uncontrolled hypercalcemia (greater than [>] 1.5 millimoles per liter [mmol/L] ionized calcium or Ca > 12 milligrams per deciliter [mg/dL] or corrected serum calcium > upper limits of normal (ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
  • Malignancies other than urothelial bladder cancer 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 less than (<) 2.5 grams per deciliter (g/dL)
  • Positive test for human immunodeficiency virus (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-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed death-1 receptor (anti-PD-1), and anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Richard Joseph, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Richard Joseph, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions