A Study to Evaluate AZD4635 with Durvalumab and with Cabazitaxel and Durvalumab in Patients with Metastatic Castra-Resistant Prostate Cancer

Overview

About this study

The purpose of this study is 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 or bone-only metastasis. 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 enrollment 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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate.
  • Known castrate-resistant disease.
  • Evidence of disease progression ≤ 6 months.
  • Body weight > 30 kg at screening.
  • illingness 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 (e.g., abiraterone acetate, enzalutamide, apalutamide, darolutamide) in either hormone-sensitive or hormone-refractory settings;
    • Prior therapy with one or more lines of taxanes (e.g., docetaxel and/or cabazitaxel);
    • Alternatively, must be taxane-ineligible;
    • Prior therapy can be in either the hormone-sensitive or the hormone-refractory setting. 
  • 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.
  • 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 (e.g., 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:

  • 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 < 50 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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Cassandra Moore, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20511107

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