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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03459846
Recruitment Status : Active, not recruiting
First Posted : March 9, 2018
Last Update Posted : February 10, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Urinary Bladder Neoplasms Drug: Durvalumab Drug: Olaparib Drug: Placebo Phase 2

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 platinum-based chemotherapy with unresectable Stage IV urothelial cancer (UC).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 154 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Platinum-Ineligible Patients With Unresectable Stage IV Urothelial Cancer
Actual Study Start Date : March 16, 2018
Actual Primary Completion Date : October 15, 2020
Estimated Study Completion Date : September 3, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Experimental: Arm 1: Durvalumab/Placebo
Durvalumab 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.
Drug: Durvalumab
Durvalumab 1500 mg IV q4w

Drug: Placebo
Matching placebo for oral tablet BID

Experimental: Arm 2: Durvalumab/Olaparib
Durvalumab 1500 mg IV q4w starting on week 1 day 1/Olaparib PO 300 mg BID adjusted based on patient's creatinine clearance.
Drug: Durvalumab
Durvalumab 1500 mg IV q4w

Drug: Olaparib
Olaparib PO 300 mg BID adjusted based on patient's creatinine clearance.




Primary Outcome Measures :
  1. The efficacy of Durvalumab+Olaparib combination therapy compared to Durvalumab + Placebo in terms of Progression-Free Survival (PFS) in patients with Platinum ineligible bladder cancer [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. The efficacy of Durvalumab+Olaparib combination therapy compared to Durvalumab + Placebo in terms of Overall survival (OS) in patients with Platinum ineligible bladder cancer [ Time Frame: 4 years ]
  2. The efficacy of Durvalumab+Olaparib combination therapy compared to Durvalumab + Placebo in terms of Duration of response (DoR) in patients with Platinum ineligible bladder cancer [ Time Frame: 2 years ]
  3. The efficacy of Durvalumab+Olaparib combination therapy compared to Durvalumab + Placebo in terms of Objective Response Rate (ORR) in patients with Platinum ineligible bladder cancer [ Time Frame: 2 years ]
  4. The efficacy of Durvalumab+Olaparib combination therapy compared to Durvalumab + Placebo in terms of Progression-Free Survival (PFS) in patients with Platinum ineligible bladder cancer with homologous recombination repair mutated (HRRm) subgroup [ Time Frame: 2 years ]
  5. The efficacy of Durvalumab+Olaparib combination therapy compared to Durvalumab + Placebo in terms of Progression free at 6 months (PFS6) in patients with Platinum ineligible bladder cancer [ Time Frame: 2 years. ]
  6. The pharmacokinetics (PK) of durvalumab and olaparib as determined by trough concentration [ 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. ]
  7. 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. ]
  8. 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. ]

Other Outcome Measures:
  1. Number of Participants with Treatment-Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: 2 years ]
  2. Changes in WHO/ECOG performance status [ Time Frame: 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 platinum-based chemotherapy defined as (i) in the opinion of the Investigator, unfit for carboplatin-based chemotherapy and (ii) 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03459846


Locations
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United States, Alabama
Research Site
Birmingham, Alabama, United States, 35294
United States, Arizona
Research Site
Goodyear, Arizona, United States, 85338
United States, Florida
Research Site
Fort Myers, Florida, United States, 33901
Research Site
Saint Petersburg, Florida, United States, 33705
Research Site
Tampa, Florida, United States, 33612
United States, Kentucky
Research Site
Louisville, Kentucky, United States, 40202
United States, New York
Research Site
Bronx, New York, United States, 10461
Research Site
Lake Success, New York, United States, 11042
Research Site
New York, New York, United States, 10065
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States, 19124
United States, Tennessee
Research Site
Nashville, Tennessee, United States, 37232
United States, Washington
Research Site
Tacoma, Washington, United States, 98405
Canada, Ontario
Research Site
Hamilton, Ontario, Canada, L8V 5C2
Research Site
Newmarket, Ontario, Canada, L3Y 2P9
Research Site
Sudbury, Ontario, Canada, P3E 5J1
Research Site
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Research Site
Montreal, Quebec, Canada, H3T 1E2
Korea, Republic of
Research Site
Incheon, Korea, Republic of, 21565
Research Site
Seoul, Korea, Republic of, 02841
Research Site
Seoul, Korea, Republic of, 03722
Research Site
Seoul, Korea, Republic of, 05505
Research Site
Seoul, Korea, Republic of, 135-710
Russian Federation
Research Site
Moscow, Russian Federation, 105077
Research Site
Moscow, Russian Federation, 125367
Research Site
Novosibirsk, Russian Federation, 630108
Research Site
Omsk, Russian Federation, 644013
Research Site
Saint Petersburg, Russian Federation, 195271
Research Site
St. Petersburg, Russian Federation, 194354
Research Site
St. Petersburg, Russian Federation, 199178
Spain
Research Site
Barcelona, Spain, 08035
Research Site
Barcelona, Spain, 08036
Research Site
Madrid, Spain, 28041
Research Site
Málaga, Spain, 29010
Research Site
Santiago de Compostela, Spain, 15706
Taiwan
Research Site
Kaohsiung, Taiwan, 807
Research Site
Kaohsiung, Taiwan
Research Site
Taichung, Taiwan, 40705
Research Site
Tainan, Taiwan, 704
Research Site
Taipei, Taiwan, 10002
Research Site
Taipei, Taiwan, 104
Research Site
Taipei, Taiwan, 112
Research Site
Taoyuan City, Taiwan, 333
Vietnam
Research Site
Hanoi, Vietnam, 100000
Research Site
Ho Chi Minh, Vietnam, 700000
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Jonathan Rosenberg, MD Memorial Sloan Kettering Cancer Center
Study Director: Mark Lanasa, MD One MedImmune Way,Gaithersburg,Maryland,United States
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03459846    
Other Study ID Numbers: D933IC00003
First Posted: March 9, 2018    Key Record Dates
Last Update Posted: February 10, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AstraZeneca:
Urinary Bladder Neoplasms
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Durvalumab
Olaparib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action