Clinical Trials /

Study of Atezolizumab as Monotherapy and in Combination With Platinum-Based Chemotherapy in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma

NCT02807636

Description:

A Phase III, randomised study of atezolizumab alone and in combination with chemotherapy versus chemotherapy alone in participants with untreated advanced urothelial cancer.

Related Conditions:
  • Renal Pelvis and Ureter Carcinoma
  • Transitional Cell Carcinoma
  • Urethral Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Atezolizumab as Monotherapy and in Combination With Platinum-Based Chemotherapy in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma
  • Official Title: A Phase III, Multicenter, Randomized, Placebo-Controlled Study of Atezolizumab (Anti−PD-L1 Antibody) as Monotherapy and in Combination With Platinum-Based Chemotherapy in Patients With Untreated Locally Advanced or Metastatic Urothelial Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: WO30070
  • SECONDARY ID: 2016-000250-35
  • NCT ID: NCT02807636

Conditions

  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
AtezolizumabTecentriqAtezolizumab+Gemcitabine+Carboplatin/Cisplatin
CarboplatinAtezolizumab+Gemcitabine+Carboplatin/Cisplatin
GemcitabineAtezolizumab+Gemcitabine+Carboplatin/Cisplatin
CisplatinAtezolizumab+Gemcitabine+Carboplatin/Cisplatin

Purpose

A Phase III, randomised study of atezolizumab alone and in combination with chemotherapy versus chemotherapy alone in participants with untreated advanced urothelial cancer.

Trial Arms

NameTypeDescriptionInterventions
Atezolizumab+Gemcitabine+Carboplatin/CisplatinExperimentalParticipants will receive blinded atezolizumab in combination with open-label platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin).
  • Atezolizumab
  • Carboplatin
  • Gemcitabine
  • Cisplatin
Placebo+Gemcitabine+Carboplatin/CisplatinPlacebo ComparatorParticipants will receive blinded placebo matched to atezolizumab in combination with open-label platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin).
  • Carboplatin
  • Gemcitabine
  • Cisplatin
Atezolizumab MonotherapyExperimentalParticipants will receive open-label atezolizumab as monotherapy.
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria

          -  Considered to be eligible to receive platinum-based chemotherapy, in the
             investigator's judgment

          -  Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to
             (</=) 2

          -  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 participants 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

          -  Measurable disease, as defined by 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, cisplatin, or gemcitabine or for 5 months 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 enrolment

          -  Active or untreated CNS metastases as determined by computed tomography (CT) or
             magnetic resonance imaging evaluation during screening and prior radiographic
             assessments

          -  Participants with treated asymptomatic central nervous system (CNS) metastases are
             eligible, provided they meet all of the following criteria: * Evaluable or measurable
             disease outside the CNS * No metastases to midbrain, pons, medulla, or within 10 mm of
             the optic apparatus (optic nerves and chiasm) * No history of intracranial or spinal
             cord hemorrhage * No ongoing requirement for corticosteroid as therapy for CNS
             disease; anti-convulsants at a stable dose are allowed * No evidence of significant
             vasogenic edema * No stereotactic radiation, whole-brain radiation or neurosurgical
             resection within 4 weeks prior to Cycle 1, Day 1 * Radiographic demonstration of
             interim stability (i.e., no progression) between the completion of CNS-directed
             therapy and the screening radiographic study * 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 Cycle 1, Day 1 or anticipated requirement for systemic
             immunosuppressive medications during the study

          -  Leptomeningeal disease

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (once monthly or more frequently)

          -  Uncontrolled tumour-related pain or hypercalcemia

          -  Significant cardiovascular disease including known left ventricular ejection fraction
             (LVEF) <40%

          -  Severe infections within 4 weeks before randomization or therapeutic oral or IV
             antibiotics within 2 weeks before randomization

          -  Major surgical procedure within 4 weeks prior to randomization or anticipation of need
             for a major surgical procedure during the course of the study other than for diagnosis

          -  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 <25 gram per liter (g/L)

          -  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 CT scan

          -  Positive test for human immunodeficiency virus (HIV)

          -  Active hepatitis B or hepatitis C

          -  Active tuberculosis

          -  Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in Participants Treated with Atezolizumab Combination Therapy Compared With Placebo Arm
Time Frame:Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (assessed at baseline, every 9 weeks for 54 weeks and every 12 weeks thereafter up to 44 months)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR) Assessed by Investigator Using RECIST v1.1
Time Frame:Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (assessed at baseline, every 9 weeks for 54 weeks and every 12 weeks thereafter up to 44 months)
Safety Issue:
Description:
Measure:Duration of response (DOR) Assessed by Investigator Using RECIST v1.1
Time Frame:From first documented objective response (CR or PR) to disease progression, death, or loss of follow-up, whichever occurs first (assessed at baseline, every 9 weeks for 54 weeks and every 12 weeks thereafter up to 44 months)
Safety Issue:
Description:
Measure:Percentage of Participants Who Were Alive at Year 1
Time Frame:Year 1
Safety Issue:
Description:
Measure:Percentage of Participants Who Were Alive and Progression Free at Year 1 Using RECIST v1.1
Time Frame:Year 1
Safety Issue:
Description:
Measure:Median Time to Deterioration in Global Health Status as Measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score
Time Frame:Cycle 1 Day 1 (cycle length = 21 days), on Day 1 of each subsequent cycle up treatment discontinuation visit (up to 44 months)
Safety Issue:
Description:
Measure:Median Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score
Time Frame:Cycle 1 Day 1 (cycle length = 21 days), on Day 1 of each subsequent cycle up treatment discontinuation visit (up to 44 months)
Safety Issue:
Description:
Measure:Maximum Atezolizumab Serum Concentration
Time Frame:Pre-dose,30 min post-end of infusion(infusion length=60min) on Cycle 1 Day 1(1 cycle=21days), pre-dose on Day 1 of Cycles 2,3,4,8 and every 8th cycle thereafter(up to 44months),120 days after last dose or treatment discontinuation visit(up to 44 months)
Safety Issue:
Description:
Measure:Minimum Atezolizumab Serum Concentration
Time Frame:Pre-dose on Day 1 (1 cycle = 21 days) of Cycles 1,2,3,4,8 and every 8th cycle thereafter (up to 44 months)
Safety Issue:
Description:
Measure:Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs)
Time Frame:Baseline up to 44 months
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS) Assessed by Investigator Using RECIST v1.1 in Participants Treated with Atezolizumab Montotherapy Compared With Placebo Arm
Time Frame:Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (assessed at baseline, every 9 weeks for 54 weeks and every 12 weeks thereafter up to 44 months)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Trial Keywords

  • Urothelial carcinoma
  • Bladder cancer
  • Anti-PD-L1
  • Transitional carcinoma
  • Tecentriq
  • Atezolizumab
  • IMvigor130

Last Updated

February 27, 2018