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Trial record 1 of 1 for:    AARDVARC
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A Study of AZD4635 With Durvalumab and With Cabazitaxel and Durvalumab in Patients With mCRPC. (AARDVARC)

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: NCT04495179
Recruitment Status : Active, not recruiting
First Posted : July 31, 2020
Last Update Posted : December 6, 2021
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

Study Description
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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).

Condition or disease Intervention/treatment Phase
Progressive Metastatic Castrate-Resistant Prostate Cancer Drug: AZD4635 Drug: Durvalumab Drug: Cabazitaxel Phase 2

Detailed Description:

This is a Phase II, international, open-label, two-arm, non-randomised study of AZD4635 in participants with mCRPC. Participants in each arm will be stratified by the presence of measurable soft tissue metastasis (per Response Evaluation Criteria in Solid Tumours [RECIST v1.1]) or bone-only metastasis (per Prostate Cancer Working Group 3 [PCWG3 criteria]). There will be no formal comparisons between treatment arms.

AZD4635 plus durvalumab (Arm A) will consist of 80 participants with mCRPC previously treated with one or more approved new hormonal agent(s) (NHAs) and one or more taxanes or participants who are taxane ineligible.

AZD4635 plus durvalumab plus cabazitaxel (Arm B) will consist of 80 participants mCRPC previously treated with docetaxel and one prior NHA.

As of November 2020, the Sponsor stopped enrolment in Arm A following decisions at the program level, not related to any safety issues. Ongoing participants in Arm A may continue treatment as planned.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : August 4, 2020
Actual Primary Completion Date : November 1, 2021
Estimated Study Completion Date : November 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A: AZD4635 + durvalumab
AZD4635 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.
 Drug: AZD4635
Subjects will receive AZD4635 orally daily

Drug: Durvalumab
Subjects will receive intravenous durvalumab every 4 weeks for Arm A and every 3 weeks for Arm B.
Experimental: Arm B: AZD4635 + durvalumab + cabazitaxel
AZD4635 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).
 Drug: AZD4635
Subjects will receive AZD4635 orally daily

Drug: Durvalumab
Subjects will receive intravenous durvalumab every 4 weeks for Arm A and every 3 weeks for Arm B.

Drug: Cabazitaxel
Subjects will receive intravenous cabazitaxel every 3 weeks


Outcome Measures
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Primary Outcome Measures :
  1. rPFS in each arm separately to determine the efficacy of AZD4635 plus durvalumab and of AZD4635 plus durvalumab plus cabazitaxel in participants with mCRPC [ Time Frame: From first dose to first documented progression or death from any cause (whichever comes first). This is expected to be an average of 5.5 months for Arm A and 11 months for Arm B ]
    rPFS is defined as the time from first dose to radiographic progression, assessed by the Investigator per RECIST 1.1 (soft tissue) and PCWG3 criteria (bone) or death from any cause, whichever occurs first.


Secondary Outcome Measures :
  1. 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 [ Time Frame: From first dose to first documented progression or death from any cause (whichever comes first). This is expected to be an average of 11 months for Arm B ]
    rPFS is defined as the time from first dose to radiographic progression, assessed by the Investigator per RECIST 1.1 (soft tissue) and PCWG3 criteria (bone) or death from any cause, whichever occurs first.

  2. 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 [ Time Frame: Arm A and B: Every 90 days from the last dose of study drug upto 2.2 years (expected) ]
    OS is defined as the time from first dose until death due to any cause regardless of whether the participant withdraws from study treatment or receives another anti-cancer therapy.

  3. Objective response rate (ORR) in each arm separately to determine the efficacy of AZD4635 plus durvalumab and of AZD4635 plus durvalumab plus cabazitaxel in participants with mCRPC [ Time Frame: From first dose to first documented progression or death from any cause (whichever comes first). This is expected to be an average of 5.5 months for Arm A and 11 months for Arm B ]
    Confirmed ORR is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) using overall radiographic response assessed by RECIST v1.1 and PCWG-3 criteria (bone), and will be based on a subset of all treated participants with measurable disease at baseline per the site Investigator.

  4. Duration of response (DoR) in each arm separately to determine the efficacy of AZD4635 plus durvalumab and of AZD4635 plus durvalumab plus cabazitaxel in participants with mCRPC [ Time Frame: From first dose to first documented progression or death from any cause (whichever comes first). This is expected to be an average of 5.5 months for Arm A and 11 months for Arm B ]
    DoR is defined as the date of first documented response (which is subsequently confirmed) until the date of documented progression or death in the absence of disease progression.

  5. Prostate-specific antigen (PSA50) response in each arm separately to determine the efficacy of AZD4635 plus durvalumab and of AZD4635 plus durvalumab plus cabazitaxel in participants with mCRPC [ Time Frame: Arm A: Screening, Day 1 of each cycle upto 11 months (expected). Duration of each cycle is 28 days; Arm B: Screening, Day 1 of each cycle upto 11 months (expected); Duration of each cycle is 28 days ]
    Confirmed PSA50 response is defined as the proportion of participants achieving a ≥50% decrease in PSA from baseline to the lowest post-baseline PSA, confirmed by a consecutive PSA at least 3 weeks later and will be based on PSA evaluable participants (dosed participants with an abnormal baseline PSA [≥1 ng/mL]).

  6. Change from baseline in worst pain, average pain and pain interference in the daily activities scales of the Brief Pain Inventory - Short Form (BPI-SF) [ Time Frame: Arm A: Screening, Day 1 of each cycle upto 12 months (expected). Duration of each cycle is 28 days; Arm B: Screening, Day 1 of each cycle upto 12 months (expected); Duration of each cycle is 28 days ]
    Worst pain, average pain and pain's interference with daily life will be assessed during the study intervention using the BPI-SF. The BPI-SF comprises a total of 15 items measuring 2 domains: pain severity and pain interference. Items measuring pain severity (including 'worst pain') are rated on an 11-point numeric rating scale (NRS)[ ranging from 0=No pain to 10=Pain as bad as you can imagine.

  7. Time to pain progression based on BPI-SF Item 3 "pain at its worst in the last 24 hours" [ Time Frame: Arm A: Screening, Day 1 of each cycle upto 12 months (expected). Duration of each cycle is 28 days; Arm B: Screening, Day 1 of each cycle upto 12 months (expected); Duration of each cycle is 28 days ]
    Pain progression will be assessed using BPI-SF.

  8. Change from baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as derived from 6 items, the FAPSI-8 from 8 items within the FACT-P and the Prostate Cancer Symptoms (PCS), from the 12 items in the prostrate-specific module of the FACT-P [ Time Frame: Arm A: Screening, Day 1 of each cycle upto 12 months (expected). Duration of each cycle is 28 days; Arm B: Screening, Day 1 of each cycle upto 12 months (expected); Duration of each cycle is 28 days ]
    The Functional Assessment of Cancer Therapy-Prostate (FACT-P) will be used to measure health related quality of life (HRQL)in men with prostate cancer. It consists of 4 subscales (physical, emotional, functional and social/family well-being) plus a 12-item prostate-specific module, the PCS subscale, which highlights concerns specific to participants with prostate cancer.

  9. Pharmacokinetic (PK) plasma concentrations for AZD4635, durvalumab and cabazitaxel [ Time Frame: Arm A: Cycle 1, 2, 3, and Cycle 4 onwards, and 90-day follow-up visit (FU) upto 14 months (expected); Arm B: Cycle 1, 2, 3, 4, 5, 7 and Cycle 11 onwards, and 90-day FU upto 14 months (expected); Cycle duration for Arm A is 28 days and Arm B is 21 days ]
    Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.

  10. Maximum observed plasma concentration (Cmax) [ Time Frame: Arm A: Cycle 1, 2, 3, and Cycle 4 onwards, and 90-day follow-up visit (FU) upto 14 months (expected); Arm B: Cycle 1, 2, 3, 4, 5, 7 and Cycle 11 onwards, and 90-day FU upto 14 months (expected); Cycle duration for Arm A is 28 days and Arm B is 21 days ]
    Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.

  11. Time to reach Cmax [ Time Frame: Arm A: Cycle 1, 2, 3, and Cycle 4 onwards, and 90-day follow-up visit (FU) upto 14 months (expected); Arm B: Cycle 1, 2, 3, 4, 5, 7 and Cycle 11 onwards, and 90-day FU upto 14 months (expected); Cycle duration for Arm A is 28 days and Arm B is 21 days ]
    Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.

  12. Time of the last measurable concentration (tlast) [ Time Frame: Arm A: Cycle 1, 2, 3, and Cycle 4 onwards, and 90-day follow-up visit (FU) upto 14 months (expected); Arm B: Cycle 1, 2, 3, 4, 5, 7 and Cycle 11 onwards, and 90-day FU upto 14 months (expected); Cycle duration for Arm A is 28 days and Arm B is 21 days ]
    Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.

  13. Terminal elimination rate constant (λz) [ Time Frame: Arm A: Cycle 1, 2, 3, and Cycle 4 onwards, and 90-day follow-up visit (FU) upto 14 months (expected); Arm B: Cycle 1, 2, 3, 4, 5, 7 and Cycle 11 onwards, and 90-day FU upto 14 months (expected); Cycle duration for Arm A is 28 days and Arm B is 21 days ]
    Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.

  14. Terminal half-life (t1/2λz) [ Time Frame: Arm A: Cycle 1, 2, 3, and Cycle 4 onwards, and 90-day follow-up visit (FU) upto 14 months (expected); Arm B: Cycle 1, 2, 3, 4, 5, 7 and Cycle 11 onwards, and 90-day FU upto 14 months (expected); Cycle duration for Arm A is 28 days and Arm B is 21 days ]
    Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.

  15. Area under the plasma concentration time curve from zero to 24 hours [AUC(0-24)], from zero to 8 hours [AUC(0-8)], from zero to the time of the last measurable concentration (AUClast), and from zero extrapolated to infinity (AUCinf) [ Time Frame: Arm A: Cycle 1, 2, 3, and Cycle 4 onwards, and 90-day follow-up visit (FU) upto 14 months (expected); Arm B: Cycle 1, 2, 3, 4, 5, 7 and Cycle 11 onwards, and 90-day FU upto 14 months (expected); Cycle duration for Arm A is 28 days and Arm B is 21 days ]
    Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.

  16. Apparent plasma clearance (CL/F for AZD4635, CL/F for cabazitaxel) [ Time Frame: Arm A: Cycle 1, 2, 3, and Cycle 4 onwards, and 90-day follow-up visit (FU) upto 14 months (expected); Arm B: Cycle 1, 2, 3, 4, 5, 7 and Cycle 11 onwards, and 90-day FU upto 14 months (expected); Cycle duration for Arm A is 28 days and Arm B is 21 days ]
    Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.

  17. Apparent volume of distribution during the terminal phase (Vz/F for AZD4635, Vz/F for cabazitaxel) [ Time Frame: Arm A: Cycle 1, 2, 3, and Cycle 4 onwards, and 90-day follow-up visit (FU) upto 14 months (expected); Arm B: Cycle 1, 2, 3, 4, 5, 7 and Cycle 11 onwards, and 90-day FU upto 14 months (expected); Cycle duration for Arm A is 28 days and Arm B is 21 days ]
    Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.

  18. Mean residence time (MRT) [ Time Frame: Arm A: Cycle 1, 2, 3, and Cycle 4 onwards, and 90-day follow-up visit (FU) upto 14 months (expected); Arm B: Cycle 1, 2, 3, 4, 5, 7 and Cycle 11 onwards, and 90-day FU upto 14 months (expected); Cycle duration for Arm A is 28 days and Arm B is 21 days ]
    Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.

  19. Number of subjects with serious and non-serious adverse events [ Time Frame: Arm A: From Screening upto 14 months (expected); Arm B: From Screening upto 14 months (expected) ]
    To assess safety and tolerability of each treatment regimen in participants with mCRPC.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 150 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed adenocarcinoma of the prostate.
  2. Known castrate-resistant disease.
  3. Evidence of disease progression ≤6 months.
  4. Body weight >30 kg at screening.
  5. Willingness to adhere to the study treatment-specific contraception requirements.
  6. Adequate bone marrow reserve and organ function.

  7. 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

  8. 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)
    • Alternatively, must be taxane-ineligible
    • Prior therapy can be in either the hormone-sensitive or the hormone-refractory setting

  9. Adequate organ function for Arm B as demonstrated by all of the following laboratory values:

    • AST and/or ALT ≤1.5 × ULN
    • TBL ≤ ULN
    • TBL ≤2.0 × ULN in the case of known Gilbert syndrome with normal direct bilirubin

  10. Participants in Arm B must have received the following prior therapy:

    • Prior docetaxel (taxane) in either hormone-sensitive or hormone-refractory settings
    • Received no prior cytotoxic chemotherapy other than docetaxel for prostate cancer except for estramustine and except adjuvant/neo-adjuvant treatment completed >3 years ago.
    • Prior therapy with only one NHAs (eg, abiraterone acetate or enzalutamide; prior apalutamide is not permitted) for treatment of mCRPC in either hormone-sensitive or hormone-refractory settings.
    • Be suitable to receive concomitant Granulocyte-colony stimulating factor during all cycles of cabazitaxel.
    • Participants who meet inclusion criteria for Arm B will be allocated preferentially to that arm until recruitment to that arm is completed.

Exclusion Criteria:

  1. Active brain metastases or leptomeningeal metastases.
  2. There must be no requirement for immunosuppressive doses of systemic corticosteroids for at least 2 weeks prior to study enrollment.
  3. 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.
  4. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases.
  5. Creatinine clearance <40 mL/min (calculated by Cockcroft-Gault equation).
  6. Prior exposure to immune-mediated therapy including.
  7. Ongoing treatment with warfarin (Coumadin).
  8. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study intervention.
Contacts and Locations
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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): NCT04495179


Locations
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United States, California
Research Site
Sacramento, California, United States, 95817
United States, Florida
Research Site
Tampa, Florida, United States, 33612
United States, Georgia
Research Site
Atlanta, Georgia, United States, 30318
United States, Missouri
Research Site
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Research Site
Winston-Salem, North Carolina, United States, 27157
Belgium
Research Site
Brasschaat, Belgium, 2930
Research Site
Gent, Belgium, 9000
France
Research Site
Bordeaux, France, 33076
Research Site
Villejuif, France, 94805
Korea, Republic of
Research Site
Goyang-si, Korea, Republic of, 10408
Research Site
Seoul, Korea, Republic of, 06351
Research Site
Seoul, Korea, Republic of, 06591
Spain
Research Site
Barcelona, Spain, 08041
Research Site
Barcelona, Spain, 8035
Research Site
Hospitalet deLlobregat, Spain, 08907
Research Site
Madrid, Spain, 28034
Sponsors and Collaborators
AstraZeneca
Parexel
Investigators
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Principal Investigator: Christopher J Sweeney, MBBS Dana-Farber Cancer Institute
More Information
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04495179    
Other Study ID Numbers: D8731C00002
2020-000209-10 ( EudraCT Number )
First Posted: July 31, 2020    Key Record Dates
Last Update Posted: December 6, 2021
Last Verified: December 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 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.
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
Keywords provided by AstraZeneca:
Prostate Cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
 Prostatic Diseases
Durvalumab
Antineoplastic Agents, Immunological
Antineoplastic Agents