Atezolizumab + Platinum-Based Chemo for Urothelial Carcinoma

A Phase III, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of Atezolizumab (Anti PD-L1 Antibody) in Combination With Gemcitabine/Carboplatin Versus Gemcitabine/Carboplatin Alone in Patients With Untreated Locally Advanced or Metastatic Urothelial Carcinoma Who Are Ineligible For Cisplatin-Based Therapy

November 22, 2017

  • Clinical Trial Information

    Trial Contact: Walton, Sherri

    Trial Phone: 321.841.1907

  • IRB No: WIRB 20160572

    Protocol Abbrev: WO30070

    Principal Investigator: Daniel Ari Landau, MD

    Sub Investigators: Hajdenberg, Julio MD

    Phase: Drug: Phase III

    Age Group: Adult

    Secondary Protocol No: WO30070

    Treatment: Oncology: Adjuvant; Oncology: 2nd line

    Applicable Disease Sites: Urothelial Carcinoma

    Therapies Involved: Atezolizumab in Combination With Gemcitabine/Carboplatin ID: NCT02807636

  • Objective

    This is a Phase III, multicenter, randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of atezolizumab in combination with gemcitabine/carboplatin versus placebo plus gemcitabine/carboplatin in participants with locally advanced or metastatic urothelial carcinoma (UC) who have not received prior systemic therapy and who are ineligible to receive cisplatin-based therapy.

  • Key Eligibility

    Inclusion Criteria:
    •   Eastern Cooperative Oncology Group [ECOG] performance status of less than or equal to (•   Histologically documented, locally advanced (T4b, any N; or any T, N2-3) or metastatic urothelial carcinoma (mUC) (M1, Stage IV) (also termed transitional cell carcinoma [TCC] or urothelial cell carcinoma [UCC] of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra)
    •   Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for central testing and determined to be evaluable for tumor PD-L1 expression prior to study enrollment; participants who have fewer than 15 unstained slides available at baseline (but no less than [<] 10) may be eligible following discussion with the Medical Monitor
    •   No prior chemotherapy for inoperable locally advanced or mUC
    •   For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a treatment-free interval more than (>) 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment naive in the metastatic setting.
    •   Prior local intravesical chemotherapy or immunotherapy is allowed if completed at least 4 weeks prior to the initiation of study treatment.
    •   Ineligible ("unfit") for cisplatin-based chemotherapy as defined by any one of the following criteria:
    o Impaired renal function (glomerular filtration rate [GFR] > 30 but < 60 mL/min); GFR should be assessed by direct measurement (i.e., creatinine clearance or thyldediaminetetra-acetate) or, if not available, by calculation from serum/plasma creatinine (Cockcroft-Gault formula)
    o CTCAE v4.0 Grade more than or equal to (>/=) 2 audiometric hearing loss of 25 dB at 2 contiguous frequencies
    o CTCAE v4.0 Grade >/=2 peripheral neuropathy (i.e., sensory alteration or paresthesias, including tingling)
    o ECOG performance status of 2
    •   Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
    •   Adequate hematologic and end-organ function
    •   For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 6 months after the last dose of carboplatin or gemcitabine or for 90 days after the last dose of atezolizumab
    •   For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm
    Exclusion Criteria:
    •   Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
    •   Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to enrollment
    •   Active or untreated CNS metastases as determined by computed tomography or magnetic resonance imaging evaluation during screening and prior radiographic assessments.
    •   Patients with treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
    o Evaluable or measurable disease outside the CNS
    o No metastases to midbrain, pons, medulla, or within 10 mm of the optic apparatus (optic nerves and chiasm)
    o No history of intracranial or spinal cord hemorrhage
    o No ongoing requirement for corticosteroid as therapy for CNS disease; anti-convulsants at a stable dose are allowed
    o No evidence of significant vasogenic edema
    o No stereotactic radiation, whole-brain radiation or neurosurgical resection within 4 weeks prior to Cycle 1, Day 1
    o Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening radiographic study
    o Screening CNS radiographic study >/=4 weeks since completion of radiotherapy or surgical resection and >/=2 weeks since discontinuation of corticosteroids
    •   Prior treatment with CD137 agonists, anti-CTLA-4, anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents
    •   Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to to Cycle 1, Day 1 or anticipated requirement for systemic immunosuppressive medications during the study
    •   Leptomeningeal disease
    •   Uncontrolled tumour-related pain or hypercalcemia
    •   Significant cardiovascular disease including known LVEF <40%
    •   Severe infections within 4 weeks before randomization or therapeutic oral or IV antibiotics within 2 weeks before randomization
    •   Malignancies other than urothelial carcinoma within 5 years prior to Cycle 1, Day 1
    •   Life expectancy of <12 weeks
    •   Pregnant or lactating, or intending to become pregnant during the study
    •   Serum albumin <2.5 gram per deci-liter (g/dL)
    •   History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    •   Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
    •   History of autoimmune disease
    •   Participants with prior allogeneic stem cell or solid organ transplantation
    •   History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
    •   Positive test for HIV
    •   Active hepatitis B or hepatitis C
    •   Active tuberculosis
    •   Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1