A Multi-arm, Open-label Phase I/IIa Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of AZD5305 in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer (PETRANHA).

Study Identifier:
D9720C00003
CT.gov Identifier:
NCT05367440
EudraCT Identifier:
2021-006289-19
EU Trial (CTIS) Number:
2023-508536-64-00
Study Contact Information:
N/A
Recruitment Complete

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Study Summary

To evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of AZD5305 when given in combination with new hormonal agents (NHAs) in patients with metastatic prostate cancer. To evaluate the combination of AZD5305 with physician’s choice of NHA including abi, darolutamide, and enzalutamide, in patients with mPC.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Prostate
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Male
    Age
    18 - 130 Years
    Study Drug
  • Drug: Experimental: Arm 1 (AZD5305 in combination with enzalutamide) Patients will receive an oral dose of AZD5305 and Enzalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur. Drug: AZD5305 Patients will receive an oral dose of AZD5305 once daily Drug: Enzalutamide Patients will receive an oral dose of Enzalutamide once daily Experimental: Arm 2 (AZD5305 in combination with abiraterone acetate) Patients will receive an oral dose of AZD5305 and Abiraterone Acetate once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur. Drug: AZD5305 Patients will receive an oral dose of AZD5305 once daily Drug: Abiraterone Acetate Patients will receive an oral dose of Abiraterone Acetate once daily Experimental: Arm 3 (AZD5305 in combination with darolutamide) Patients will receive an oral dose of AZD5305 once daily and Darolutamide twice daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur. Drug: AZD5305 Patients will receive an oral dose of AZD5305 once daily Drug: Darolutamide Patients will receive an oral dose of Darolutamide twice daily Arm 1: AZD5305 in combination with enzalutamide Arm 2: AZD5305 in combination with abiraterone acetate Arm 3: AZD5305 in combination with darolutamide Experimental: Arm 4 (AZD5305 in combination with apalutamide) Patients will receive an oral dose of AZD5305 and Apalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur. Drug: Apalutamide Patients will receive an oral dose of Apalutamide once daily The study consists of 2 parts, Part A and Part B. Part A consists of the dose escalation cohorts and will include patients with metastatic castration resistant prostate cancer (mCRPC) or metastatic castration-sensitive prostate cancer (mCSPC); Part B consists of dose expansion cohorts and will include patients with mCSPC only. Part A comprises 3 individual arms each evaluating the safety, tolerability, and preliminary efficacy of AZD5305 in combination with a specific new hormonal agent (NHA). Part B comprises up to 3 individual arms (arms to be opened at Sponsor's discretion) each investigating the preliminary efficacy and aims to further build on the safety data for the combination of AZD5305 with a specific NHA. Approximately 520 patients will be enrolled and screened to ensure the required number of evaluable patients in each part and arm are enrolled. For Part A, 300 patients may be screened to obtain up to approximately 252 patients that can be assigned to study treatments across all study arms (1 to 3). For Part B dose expansion cohorts, up to 220 patients may be screened to obtain up to approximately 180 patients that can be assigned to study treatments across all study arms (1 to 3). Study treatment administration will continue until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur. Pts, allocated by investigator choice, received saruparib 60 mg once daily (OD) + enzalutamide 160 mg OD (Arm 1), abiraterone 1000 mg OD + 5 mg prednisone OD or twice daily (BD; Arm 2), or darolutamide 600 mg BD (Arm 3) until disease progression or intolerable adverse event (AE). Arm 4 (+ apalutamide 240 mg OD).
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • For whole study:
    • Age ≥ 18 at the time of screening.
    • Histologically confirmed diagnosis of metastatic prostate cancer.
    • Candidate for treatment with enzalutamide, abiraterone acetate, or darolutamide with documented current evidence of metastatic prostate cancer.
    • Surgically or medically castrated.
    • Adequate organ and marrow function.
    • Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0-1 with no deterioration over the previous 2 weeks.
    • Life expectancy ≥ 16 weeks.
    • Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to approximately 6 months after the last dose of study treatment .
    • For Patients Recruited Specifically to tumour Pharmacodynamic Cohorts:
    • • Patients must have at least 1 tumour suitable for paired biopsies
    • For Part A:
    • • Patients with Metastatic Castrate ion-Resistant Prostate Cancer (mCRPC) or Metastatic Castration Sensitive Prostate Cancer (mCSPC).
    • For Part B:
    • • Patients must have mCSPC (de novo or recurrent) with a baseline PSA value of ≥ 0.2 ng/mL
    • Pts were aged ≥18 years with histologically confirmed mCRPC or metastatic castration-sensitive prostate cancer (mCSPC), suitable for NHA treatment, with or without HRR mutations in tumor tissue
    Exclusion criteria
    • For Part A mCRPC patients only:
    • Any previous treatment with a new hormonal agent (NHA), poly (adenosine diphosphateribose) polymerase inhibitor (PARPi), Lutetium prostate-specific membrane antigen (Lu-PSMA), platinum chemotherapy
    • Patients recruited to the PDc cohorts should not have received a prior use of new hormonal agents (NHA).
    • Any previous treatment with a PARP inhibitor, platinum, NHA, Immuno-oncology (IO), radiopharmaceutical therapy, or prior treatment with docetaxel in mCSPC setting.
    • Concomitant use of medications or herbal supplements known to be:
    • Strong and moderate CYP3A4 inducers/inhibitors (applies for all arms)
    • For Arm 1 (enzalutamide) patients: Strong CYP2C8 inhibitors
    • For Arm 3 (darolutamide) patients: Strong P-glycoprotein inducers
    • Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
    • Treatment with any of the following:
    • Any investigational agents or study interventions from a previous clinical study within 5 half lives or 3 weeks (whichever is longer) of the first dose of study treatment.
    • Any other anticancer treatment within the following time periods prior to the first dose of study treatment: (i) Cytotoxic and non-cytotoxic treatment: 3 weeks or 5 half-lives (whichever is shorter). (ii) Biological products including immuno-oncology agents: 4 weeks before enrolment.
    • Any live virus or bacterial vaccine within 28 days of the first dose of study treatment.
    • Any concurrent anticancer therapy or concurrent use of prohibited medications.
    • Major surgery within 4 weeks prior to the first dose of study treatment.
    • Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment.
    • With the exception of alopecia, and peripheral neuropathy; any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of study enrolment.
    • Any history of persisting (> 2 weeks) severe pancytopenia.
    • Spinal cord compression, or brain metastases unless asymptomatic and treated and stable.
    • Any evidence of severe or uncontrolled systemic diseases, including, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
    • Patients with any known predisposition to bleeding (eg, active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy.
    • Any clinically significant cardiac disorders including QT prolongation, abnormal electrocardiogram (ECG).
    • Any clinically significant cardiovascular diseases including symptomatic heart failure, uncontrolled hypertension, acute coronary syndrome, cardiomyopathy, valvular heart disease, atrial fibrillation, stroke.
    • Patients with history of myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML).
    • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection.
    • Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
    • Any condition that would interfere with evaluation of the study treatment or interpretation of patient safety or study results.
    • Uncontrolled intercurrent illness within the last 12 months, including but not limited to, active interstitial lung disease, serious chronic gastrointestinal (GI) conditions associated with diarrhoea, or psychiatric illness/social situations
    • History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study treatment and of low potential risk for recurrence.
    • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
    • Arm 1 (Enzalutamide) only: History of seizure or any condition that may predispose to seizure (eg, prior cortical stroke, significant brain trauma).
    • Arm 2 (Abiraterone acetate) only: (i) Active infection or other medical condition that would contraindicate the use of systemic steroids (prednisone/prednisolone). (ii) Low serum potassium (< 3.5 mmol/L). (iii) History of uncontrolled pituitary or adrenal dysfunction.
    • Key exclusion criteria were previous PARPi, platinum chemotherapy, or targeted radioligand therapy for pts with mCRPC or mCSPC; and previous NHA or docetaxel in pts with mCSPC

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Carolinas
    Myrtle Beach, SC, United States, 29572
    Investigator
    Neal Shore
    Status
    Recruiting
    Condition(s) Treated at Site
    Prostate