A Study of AZD4635 With Durvalumab and With Cabazitaxel and Durvalumab in Patients With mCRPC.
AARDVARC
A Phase II, Open-label, Study to Assess the Efficacy, Safety, and Tolerability of AZD4635 in Combination With Durvalumab and in Combination With Cabazitaxel and Durvalumab in Patients Who Have Progressive Metastatic Castrate-Resistant Prostate Cancer (AARDVARC)
2 other identifiers
interventional
30
5 countries
16
Brief Summary
This is a Phase II, international, open-label, two-arm, non-randomised study of AZD4635 in participants with metastatic castration-resistant prostate cancer (mCRPC).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Aug 2020
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 23, 2020
CompletedFirst Posted
Study publicly available on registry
July 31, 2020
CompletedStudy Start
First participant enrolled
August 4, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
August 8, 2022
CompletedResults Posted
Study results publicly available
August 9, 2023
CompletedAugust 9, 2023
July 1, 2023
1.2 years
July 23, 2020
October 27, 2022
July 21, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Radiographic Progression Free Survival (rPFS) in Each Arm Separately to Determine the Efficacy of AZD4635 Plus Durvalumab and of AZD4635 Plus Durvalumab Plus Cabazitaxel in Patients With Metastatic Castrate-resistant Prostate Cancer (mCRPC)
rPFS was defined as the time from first dose to radiographic progression, assessed by the Investigator per RECIST 1.1 (soft tissue) and PCWG3 (Prostate Cancer Working Group 3) criteria \[bone\] or death from any cause, whichever occurred first.
From first dose to first documented progression or death from any cause (whichever comes first) (approximately 1 year)
Secondary Outcomes (16)
rPFS by Adenosine (ADO) Signalling Gene Expression in High and Low Subgroups to Determine the Efficacy of AZD4635 Plus Durvalumab Plus Cabazitaxel in Participants With mCRPC
From first dose to first documented progression or death from any cause (whichever comes first), up to two years
Overall Survival (OS) in Each Arm Separately to Determine the Efficacy of AZD4635 Plus Durvalumab and of AZD4635 Plus Durvalumab Plus Cabazitaxel in Participants With mCRPC
Arm A and B: Every 90 days from the last dose of study drug up to 2 years
Number of Participants With Objective Response in Subjects With MCRPC Who Received AZD4635 Plus Durvalumab Plus Cabazitaxel
From first dose to first documented progression or death from any cause (whichever comes first), up to two years
Number of Participants With Prostate-specifin Antigen (PSA50) Response in Subjects With MCRPC Who Received AZD4635 Plus Durvalumab Plus Cabazitaxel
Arm A: Screening, Day 1 of each cycle up to 11 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 11 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF)
Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
- +11 more secondary outcomes
Study Arms (2)
Arm A: AZD4635 + durvalumab
EXPERIMENTALAZD4635 plus durvalumab (Arm A) will consist of participants with mCRPC previously treated with one or more approved NHAs (eg, abiraterone acetate, enzalutamide, apalutamide and/or darolutamide), and one or more taxanes, or participants who are taxane ineligible.
Arm B: AZD4635 + durvalumab + cabazitaxel
EXPERIMENTALAZD4635 plus durvalumab plus cabazitaxel (Arm B) will consist of participants with mCRPC previously treated with docetaxel and one prior NHA (either abiraterone acetate or enzalutamide but not both (prior apalutamide is not allowed in Arm B).
Interventions
Subjects will receive AZD4635 orally daily
Subjects will receive intravenous durvalumab every 4 weeks for Arm A and every 3 weeks for Arm B.
Subjects will receive intravenous cabazitaxel every 3 weeks
Eligibility Criteria
You may qualify if:
- Histologically confirmed adenocarcinoma of the prostate.
- Known castrate-resistant disease.
- Evidence of disease progression ≤6 months.
- Body weight \>30 kg at screening.
- Willingness to adhere to the study treatment-specific contraception requirements.
- Adequate bone marrow reserve and organ function.
- Adequate organ function for Arm A as demonstrated by all of the following laboratory values:
- Alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) if no demonstrable liver metastases or ≤5 × ULN in the presence of liver metastases.
- Aspartate aminotransferase (AST) ≤2.5 × ULN if no demonstrable liver metastases or ≤5 × ULN in the presence of liver metastases
- Total bilirubin (TBL) ≤1.5 × ULN
- TBL ≤2.0 × ULN in the case of known Gilbert syndrome with normal direct bilirubin
- Participants in Arm A must have received the following prior therapy:
- Maximum of 3 lines of therapy in the mCRPC setting
- Prior therapy with one or more NHAs (eg, abiraterone acetate, enzalutamide, apalutamide, darolutamide) in either hormone-sensitive or hormone-refractory settings
- Prior therapy with one or more lines of taxanes (eg, docetaxel and/or cabazitaxel)
- +11 more criteria
You may not qualify if:
- Active brain metastases or leptomeningeal metastases.
- There must be no requirement for immunosuppressive doses of systemic corticosteroids for at least 2 weeks prior to study enrollment.
- History of pneumonitis requiring corticosteroids, second malignancy that is progressing and/or received active treatment ≤3 years before the first dose of study intervention, and hypersensitivity to polysorbate-80 if allocated to cabazitaxel.
- As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases.
- Creatinine clearance \<40 mL/min (calculated by Cockcroft-Gault equation).
- Prior exposure to immune-mediated therapy including.
- Ongoing treatment with warfarin (Coumadin).
- Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study intervention.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Parexelcollaborator
Study Sites (16)
Research Site
Sacramento, California, 95817, United States
Research Site
Tampa, Florida, 33612, United States
Research Site
Atlanta, Georgia, 30318, United States
Research Site
St Louis, Missouri, 63110, United States
Research Site
Winston-Salem, North Carolina, 27157, United States
Research Site
Brasschaat, 2930, Belgium
Research Site
Ghent, 9000, Belgium
Research Site
Bordeaux, 33076, France
Research Site
Villejuif, 94805, France
Research Site
Goyang-si, 10408, South Korea
Research Site
Seoul, 06351, South Korea
Research Site
Seoul, 06591, South Korea
Research Site
Barcelona, 08041, Spain
Research Site
Barcelona, 8035, Spain
Research Site
Hospitalet deLlobregat, 08907, Spain
Research Site
Madrid, 28034, Spain
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Head
- Organization
- AstraZeneca Clinical Study Information Center
Study Officials
- PRINCIPAL INVESTIGATOR
Christopher J Sweeney, MBBS
Dana-Farber Cancer Institute
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 23, 2020
First Posted
July 31, 2020
Study Start
August 4, 2020
Primary Completion
November 1, 2021
Study Completion
August 8, 2022
Last Updated
August 9, 2023
Results First Posted
August 9, 2023
Record last verified: 2023-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, 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 de-identified 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.
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.