Clinical trial NCT03459846: A Study of Durvalumab Alone and Durvalumab+Olaparib in Advanced, Platinum-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 Platinum-Ineligible Patients With Unresectable Stage IV Urothelial Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Urinary Bladder Neoplasms
Keywords: Urinary Bladder Neoplasms
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-03-09
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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).

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 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 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.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: 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 outcomes:
measure: Overall Survival (OS)
timeFrame: 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
measure: Objective Response Rate (ORR)
timeFrame: 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
measure: Duration of Response (DoR)
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Goodyear
country: United States
facility: Research Site
state: Arizona
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Bronx
country: United States
facility: Research Site
state: New York
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Newmarket
country: Canada
facility: Research Site
state: Ontario
city: Sudbury
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan City
country: Taiwan
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh city
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Jonathan Rosenberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: One MedImmune Way,Gaithersburg,Maryland,United States
name: Mark Lanasa, MD
role: STUDY_DIRECTOR
References: