Clinical Trials /

A Study of Durvalumab Alone and Durvalumab+Olaparib in Advanced, Platinum-Ineligible Bladder Cancer (BAYOU)

NCT03459846

Description:

A Phase II, Randomized, Multi-Center, Double-Blind, Comparative Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Olaparib for First-Line Treatment in Platinum-Ineligible Patients With Unresectable Stage IV Urothelial Cancer

Related Conditions:
  • Bladder Carcinoma
  • Bladder Urothelial Carcinoma
  • Infiltrating Renal Pelvis and Ureter Urothelial Carcinoma
  • Renal Pelvis Urothelial Carcinoma
  • Renal Pelvis and Ureter Carcinoma
  • Ureter Urothelial Carcinoma
  • Urethral Carcinoma
  • Urethral Urothelial Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase II Study of Durvalumab and Olaparib in Advanced, Cisplatin Ineligible Bladder Cancer (BAYOU)
  • Official Title: A Phase II, Randomized, Multi-Center, Double-Blind, Comparative Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Olaparib for First-Line Treatment in Cisplatin-Ineligible Patients With Unresectable Stage IV Urothelial Cancer

Clinical Trial IDs

  • ORG STUDY ID: D933IC00003
  • NCT ID: NCT03459846

Conditions

  • Urinary Bladder Neoplasms

Interventions

DrugSynonymsArms
DurvalumabArm 1: Durvalumab/Placebo
OlaparibArm 2: Durvalumab/Olaparib
PlaceboArm 1: Durvalumab/Placebo

Purpose

A Phase II, Randomized, Multi-Center, Double-Blind, Comparative Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Olaparib for First-Line Treatment in Cisplatin-Ineligible Patients With Unresectable Stage IV Urothelial Cancer

Detailed Description

      This is a Phase II, randomized, double-blind, placebo controlled, multi-center, comparative
      global study to determine the efficacy and safety of durvalumab + olaparib combination
      therapy versus durvalumab + placebo (durvalumab monotherapy) as first-line treatment in
      patients ineligible for cisplatin with unresectable Stage IV urothelial cancer (UC). A
      biomarker enriched study design will be employed to evaluate the efficacy and safety of the
      study treatment arms in both homologous recombination repair mutated (HRRm) and HRR wild-type
      (HRRwt) patients.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1: Durvalumab/PlaceboExperimentalDurvalumab 1500 mg intravenous (IV) every 4 weeks (q4w) starting on week 1 day 1/Placebo orally (PO) twice a day (BID) starting on week 1 day 1.
  • Durvalumab
  • Placebo
Arm 2: Durvalumab/OlaparibExperimentalDurvalumab 1500 mg IV q4w starting on week 1 day 1/Olaparib PO 300 mg BID adjusted based on patient's creatinine starting on week 1 day 1.
  • Durvalumab
  • Olaparib

Eligibility Criteria

        Inclusion criteria:

          1. Provision of signed and dated, written ICF

          2. Histologically or cytologically documented TCC/UC of the urothelium (including renal
             pelvis, ureters, urinary bladder, and urethra) also meeting the following:
             Unresectable, Stage IV disease; No prior systemic therapy for unresectable, Stage IV
             disease.

          3. Ineligible for cisplatin-based chemotherapy defined as meeting one of the following
             criteria: CrCl <60 mL/min calculated by Cockcroft-Gault equation; Common Terminology
             Criteria for Adverse Events (CTCAE) Grade ≥2 audiometric hearing loss (25 dB in 2
             consecutive wave ranges); CTCAE Grade ≥2 peripheral neuropathy; New York Heart
             Association Class III heart failure; ECOG 2.

          4. Known tumor HRR mutation status prior to randomization.

          5. World Health Organization (WHO)/ECOG performance status of 0, 1, or 2.

          6. Patients with at least 1 RECIST 1.1 target lesion at baseline.

          7. Ability to swallow oral medications.

          8. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for
             female pre-menopausal patients.

        Exclusion criteria

          1. Active or prior documented autoimmune or inflammatory disorders.

          2. Other invasive malignancy within 5 years before the first dose of the IP.

          3. Major surgical procedure within 28 days prior to the first dose

          4. Brain metastases or spinal cord compression unless the patient's condition is stable
             and off steroid for at least 14 days

          5. History of active primary immunodeficiency.

          6. Active infection including tuberculosis (TB)

          7. History of allogenic organ transplantation.

          8. Uncontrolled intercurrent illness

          9. Prior exposure to a PARP inhibitor or immune-mediated therapy.

         10. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.

         11. Current or prior use of immunosuppressive medication within 14 days before the first
             dose of the IP.

         12. No radiation therapy is allowed, unless it is (1) definitive radiation that had been
             administered at least 12 months prior; (2) palliative radiation to the brain, with
             associated criteria for stability or lack of symptoms; or (3) palliative radiation to
             painful bony lesions (this must comprise less than 30% of the bone marrow) or
             symptomatic pelvic soft tissue mass(es).

         13. Receipt of live attenuated vaccine within 30 days prior to the first dose of the IP.

         14. Patients with a known hypersensitivity to durvalumab, olaparib, or any of the
             excipients of the products.

         15. Female patients who are pregnant or breastfeeding or male or female patients of
             reproductive potential who are not willing to employ effective birth control from
             screening to 90 days after the last dose of durvalumab.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The efficacy of Durvalumab+Olaparib combination therapy compared to Durvalumab + Placebo in terms of Progression-Free Survival (PFS) in patients with cisplatin ineligible bladder cancer
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:The efficacy of Durvalumab+Olaparib combination therapy compared to Durvalumab + Placebo in terms of Overall survival (OS) in patients with cisplatin ineligible bladder cancer
Time Frame:4 years
Safety Issue:
Description:
Measure:The efficacy of Durvalumab+Olaparib combination therapy compared to Durvalumab + Placebo in terms of Duration of response (DoR) in patients with cisplatin ineligible bladder cancer
Time Frame:4 years
Safety Issue:
Description:
Measure:The efficacy of Durvalumab+Olaparib combination therapy compared to Durvalumab + Placebo in terms of Objective Response Rate (ORR) in patients with cisplatin ineligible bladder cancer
Time Frame:4 years
Safety Issue:
Description:
Measure:The efficacy of Durvalumab+Olaparib combination therapy compared to Durvalumab + Placebo in terms of Progression-free at 6 months (APF6) in patients with cisplatin ineligible bladder cancer
Time Frame:6 months.
Safety Issue:
Description:
Measure:Concentration of durvalumab and olaparib
Time Frame:Concentration of durvalumab and olaparib will be assessed three times, in Cycle 1 (each cycle is 28 days), 2 and 4. Additional assessments at Day 30 post last dose for olaparib, 3 months post last dose for durvalumab.
Safety Issue:
Description:
Measure:Presence of anti-drug antibodies (ADA) for durvalumab
Time Frame:ADA for durvalumab will be assessed three times, in Cycle 1(each cycle is 28 days), 2 and 4, and 3 and 6 months post last dose of durvalumab.
Safety Issue:
Description:
Measure:Patient reported outcome (PRO) including Global health status/Quality of Life (QoL), assessed through questionnaire - European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC QLQ-C30)
Time Frame:PRO:Global health status assessment on day of first dose and every 4 weeks until 3 months post treatment discontinuation.
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Urinary Bladder Neoplasms

Last Updated

March 21, 2018