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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03459846
• Collaborator: (none)
• Enrollment: 154
• Locations: 45
• Arms: 2
• Anticipated Duration (Months): 65.6
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Study Design

• Study Type: Interventional
• 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: Mar 16, 2018
• Actual Primary Completion Date: Oct 15, 2020
• Anticipated Study Completion Date: Sep 4, 2023

Arms and Interventions

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.

Outcome Measures

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 [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 [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 [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 [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 [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 [2 years.]

6. The pharmacokinetics (PK) of durvalumab and olaparib as determined by trough concentration [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 [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) [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) [2 years]

2. Changes in WHO/ECOG performance status [2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 130 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35294
2	Research Site	Goodyear	Arizona	United States	85338
3	Research Site	Fort Myers	Florida	United States	33901
4	Research Site	Saint Petersburg	Florida	United States	33705
5	Research Site	Tampa	Florida	United States	33612
6	Research Site	Louisville	Kentucky	United States	40202
7	Research Site	Bronx	New York	United States	10461
8	Research Site	New Hyde Park	New York	United States	11042
9	Research Site	New York	New York	United States	10065
10	Research Site	Philadelphia	Pennsylvania	United States	19124
11	Research Site	Nashville	Tennessee	United States	37232
12	Research Site	Tacoma	Washington	United States	98405
13	Research Site	Hamilton	Ontario	Canada	L8V 5C2
14	Research Site	Newmarket	Ontario	Canada	L3Y 2P9
15	Research Site	Sudbury	Ontario	Canada	P3E 5J1
16	Research Site	Toronto	Ontario	Canada	M5G 2M9
17	Research Site	Montreal	Quebec	Canada	H3T 1E2
18	Research Site	Incheon		Korea, Republic of	21565
19	Research Site	Seoul		Korea, Republic of	02841
20	Research Site	Seoul		Korea, Republic of	03722
21	Research Site	Seoul		Korea, Republic of	05505
22	Research Site	Seoul		Korea, Republic of	135-710
23	Research Site	Moscow		Russian Federation	105077
24	Research Site	Moscow		Russian Federation	125367
25	Research Site	Novosibirsk		Russian Federation	630108
26	Research Site	Omsk		Russian Federation	644013
27	Research Site	Saint Petersburg		Russian Federation	195271
28	Research Site	St. Petersburg		Russian Federation	194354
29	Research Site	St. Petersburg		Russian Federation	199178
30	Research Site	Barcelona		Spain	08036
31	Research Site	Madrid		Spain	08035
32	Research Site	Madrid		Spain	28041
33	Research Site	Málaga		Spain	29010
34	Research Site	Santiago de Compostela		Spain	15706
35	Research Site	Kaohsiung		Taiwan	807
36	Research Site	Kaohsiung		Taiwan
37	Research Site	Taichung		Taiwan	40705
38	Research Site	Tainan		Taiwan	704
39	Research Site	Taipei		Taiwan	10002
40	Research Site	Taipei		Taiwan	104
41	Research Site	Taipei		Taiwan	112
42	Research Site	Taoyuan City		Taiwan	333
43	Research Site	Hanoi		Vietnam	100000
44	Research Site	Ho Chi Minh city		Vietnam	700000
45	Research Site	Ho Chi Minh		Vietnam	700000

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Jonathan Rosenberg, MD, Memorial Sloan Kettering Cancer Center
• Study Director: Mark Lanasa, MD, One MedImmune Way,Gaithersburg,Maryland,United States

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info
• Related Info

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03459846
• Other Study ID Numbers: D933IC00003
• First Posted: Mar 9, 2018
• Last Update Posted: Mar 3, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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: Urinary Bladder Neoplasms; Durvalumab; Olaparib

Study Results

No Results Posted as of Mar 3, 2022