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

Study Overview
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Brief Summary
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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

Detailed Description
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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).

Official Title
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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

Conditions
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Urinary Bladder Neoplasms

Intervention / Treatment
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* Drug: Durvalumab
* Drug: Olaparib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Provision of signed and dated, written ICF 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. 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. Known tumor HRR mutation status prior to randomization. World Health Organization (WHO)/ECOG performance status of 0, 1, or 2. Patients with at least 1 RECIST 1.1 target lesion at baseline. Ability to swallow oral medications. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Exclusion criteria Active or prior documented autoimmune or inflammatory disorders. Other invasive malignancy within 5 years before the first dose of the IP. Major surgical procedure within 28 days prior to the first dose Brain metastases or spinal cord compression unless the patient's condition is stable and off steroid for at least 14 days History of active primary immunodeficiency. Active infection including tuberculosis (TB) History of allogenic organ transplantation. Uncontrolled intercurrent illness Prior exposure to a PARP inhibitor or immune-mediated therapy. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Current or prior use of immunosuppressive medication within 14 days before the first dose of the IP. 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). Receipt of live attenuated vaccine within 30 days prior to the first dose of the IP. Patients with a known hypersensitivity to durvalumab, olaparib, or any of the excipients of the products. 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 and 6 months for participants taking also Olaparib in case of female participants, 90 days after receipt of the last dose of the IP in case of male participants.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Durvalumab/Placebo<br>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<br>* Durvalumab 1500 mg IV q4w<br>Drug: Placebo<br>* Matching placebo for oral tablet BID<br>|
| Experimental: Arm 2: Durvalumab/Olaparib<br>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<br>* Durvalumab 1500 mg IV q4w<br>Drug: Olaparib<br>* Olaparib PO 300 mg BID adjusted based on patient's creatinine clearance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Progression-free survival based on investigator assessments according to RECIST 1.1 | Assessments performed at baseline and every 8 weeks from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), assessed up to the data cut-off date (15 Oct 2020), up to a max. of 31 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Number of Participants with Overall Survival (OS), where OS was defined as the time from the date of randomization until death due to any cause. | From the date of randomization until the death due to any cause, assessed up to the data cut-off date (15 October 2020), to a maximum of 31 months | 
| Objective Response Rate (ORR) | ORR (per RECIST 1.1 using Investigator assessments) is defined as the number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions; PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters | From the date of randomization to the date of progression or the last evaluable assessment in the absence of progression, assessed up to the data cut-off date (15 October 2020), to a maximum of 31 months | 
| Duration of Response (DoR) | Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. DoR is the time from the date of first documented response until the date of documented progression or death in the absence of disease progression | Tumor assessments every 8 weeks after randomization for the first 48 weeks and then every 12 weeks thereafter until the date of objective disease progression. Assessed up to the data cut-off date (15 October 2020), to a maximum of 31 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urinary Bladder Neoplasms