Metastatic Prostate CancerPhase 1/2PETRANHANCT05367440
Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer
A Phase 1/2 study testing AZD5305, Enzalutamide and Abiraterone Acetate in people with Metastatic Prostate Cancer, run by AstraZeneca at 20 sites in 4 countries.
Trial summary
This study will 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. Read more about this study
- Who is it for?
- Ages 18 to 130 years, men only
- Conditions the study is for
- Metastatic Prostate Cancer
- What is being tested?
- AZD5305, Enzalutamide and Abiraterone Acetate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 174 participants
- Where
- 20 sitesin 4 countries
- Study dates
- 2 Jun 2022to 11 Apr 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For whole study:
- Age ≥ 18 at the time of screening.
- Histologically confirmed diagnosis of metastatic prostate cancer.
- Candidate for treatment with enzalutamide, abiraterone acetate, darolutamide or apalutamide with documented current evidence of metastatic prostate cancer.
- Surgically or medically castrated.
- Adequate organ and marrow function.
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- 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
Who cannot join
- 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).
- For Part A and Part B mCSPC Patients:
- Any previous treatment with a PARPi, 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:
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- 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) and Arm 4 (Apalutamide): 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.
- Arm 4 (Apalutamide): (i) Moderate or severe skin conditions or diseases that could affect the skin (eg. scleroderma, lupus). (ii) Any skin or medical condition that in the Investigator's opinion could increase the risk of skin toxicity.
Trial locations and contacts
20 sites in 4 countries.
20 sites in 4 countries
United States6 sites
Research Site
Detroit, Michigan, 48201
Research Site
Detroit, Michigan, 48202
Research Site
Houston, Texas, 77030
Research Site
Houston, Texas, 77094
Research Site
Myrtle Beach, South Carolina, 29572
Research Site
Syracuse, New York, 13210
Australia6 sites
Research Site
Camperdown, 2050
Research Site
Darlinghurst, 2010
Research Site
East Melbourne, 3002
Research Site
Heidelberg, 3084
Research Site
Melbourne, 3004
Research Site
St Leonards, 2065
Italy4 sites
Research Site
Candiolo, 10060
Research Site
Milan, 20133
Research Site
Orbassano, 10043
Research Site
Padova, 35128
United Kingdom4 sites
Research Site
Cambridge, CB2 0QQ
Research Site
Glasgow, G12 0YN
Research Site
Manchester, M20 4BX
Research Site
Plymouth, PL6 8DH
About this study
Official title: 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)
This study will 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.
Read the detailed description
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 4 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 4 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 783 patients will be enrolled and screened to ensure the required number of evaluable patients in each part and arm are enrolled. For Part A, 356 patients may be screened to obtain up to approximately 308 patients that can be assigned to study treatments across all study arms (1 to 4). For Part B dose expansion cohorts, up to 427 patients may be screened to obtain up to approximately 360 patients that can be assigned to study treatments across all study arms (1 to 4).
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.
- Conditions
- Metastatic Prostate Cancer
- Being tested
- AZD5305, Enzalutamide, Abiraterone Acetate, Darolutamide, Apalutamide
- Keywords
- PETRANHA, AZD5305, New Hormonal Agents
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD5305Drug
Patients will receive an oral dose of AZD5305 once daily
EnzalutamideDrug
Also called Xtandi
Patients will receive an oral dose of Enzalutamide once daily
Abiraterone AcetateDrug
Also called Zytiga
Patients will receive an oral dose of Abiraterone Acetate once daily
DarolutamideDrug
Also called Nubeqa
Patients will receive an oral dose of Darolutamide twice daily
ApalutamideDrug
Also called Erleada
Patients will receive an oral dose of Apalutamide once daily
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (AZD5305 in combination with enzalutamide) | Experimental | 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. Receives: Drug: AZD5305; Drug: Enzalutamide |
| Arm 2 (AZD5305 in combination with abiraterone acetate) | Experimental | 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. Receives: Drug: AZD5305; Drug: Abiraterone Acetate |
| Arm 3 (AZD5305 in combination with darolutamide) | Experimental | 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. Receives: Drug: AZD5305; Drug: Darolutamide |
| Arm 4 (AZD5305 in combination with apalutamide) | Experimental | 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. Receives: Drug: Apalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with Adverse Events and Serious Adverse Events
Number of patients with adverse events and with serious adverse events including abnormal clinical observations, abnormal ECG parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline will be assessed.
Measured: Up to post treatment follow-up (28 days after last dose) [assessed up to 2.3 years]
Part A: Number of patients with Dose Limiting Toxicities (DLTs)
To assess the safety and tolerability of AZD5305 when given in combination with NHA.
Measured: For Arm 1: 35 days, For Arm 2 and 3: 28 days
Secondary outcomes (22)
Area Under the concentration Curve (AUC) of AZD5305
To characterise the PK (AUC) of AZD5305 at steady state after multiple dosing of AZD5305 monotherapy.
Measured: At the end of Cycle 0 (Cycle 0 is of 7 days)
Maximum plasma concentration (Cmax) of AZD5305
To characterise the PK (Cmax) of AZD5305 at steady state after multiple dosing of AZD5305 monotherapy.
Measured: At the end of Cycle 0 (Cycle 0 is of 7 days)
Time to maximum concentration (tmax) of AZD5305
To characterise the PK (tmax) of AZD5305 at steady state after multiple dosing of AZD5305 monotherapy.
Measured: At the end of Cycle 0 (Cycle 0 is of 7 days)
AUC of AZD5305
To characterise the PK (AUC) of AZD5305 following oral dose administration of AZD5305 in combination with NHA.
Measured: Arm 1: At Cycle 1 Day 1, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8, and Cycle 3 Day 1; Arm 2 and 3: At Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Each Cycle is of 28 days)
Cmax of AZD5305
To characterise the PK (Cmax) of AZD5305 following oral dose administration of AZD5305 in combination with NHA.
Measured: Arm 1: At Cycle 1 Day 1, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8, and Cycle 3 Day 1; Arm 2 and 3: At Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Each Cycle is of 28 days)
tmax of AZD5305
To characterise the PK (tmax) of AZD5305 following oral dose administration of AZD5305 in combination with NHA.
Measured: Arm 1: At Cycle 1 Day 1, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8, and Cycle 3 Day 1; Arm 2 and 3: At Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Each Cycle is of 28 days)
Objective response rate (ORR)
To assess the preliminary antitumour activity of AZD5305 in combination with NHA. ORR will be assessed as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (soft tissue) and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) and is defined as the percentage of patients who have a confirmed visit response of complete response (CR) or partial response (PR) in their soft tissue disease and no disease progression in their bone scan.
Measured: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Duration of response (DoR)
To assess the preliminary antitumour activity of AZD5305 in combination with NHA. DoR is defined as the time from the date of first documented response (which is subsequently confirmed) until date of documented progression or death in the absence of progressive disease (PD).
Measured: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Time to response (TTR)
To assess the preliminary antitumour activity of AZD5305 in combination with NHA. TTR is defined as the time from first dose until the first documentation of a subsequently confirmed objective response.
Measured: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Radiographic progression-free survival (rPFS)
To assess the preliminary antitumour activity of AZD5305 in combination with NHA. rPFS is defined as the time from start of first treatment until progression as per RECIST v1.1 (soft tissue) and PCWG3 criteria (bone) or death from any cause.
Measured: From Screening (Day -28), 12 months, 24 months and up to confirmed disease progression [assessed up to 2.3 years]
Percentage change in tumour size
To assess the preliminary antitumour activity of AZD5305 in combination with NHA. Percentage change in tumour size will be determined for patients with measurable disease at baseline.
Measured: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Number of patients with ≥ 50% prostate-specific antigen (PSA) decrease from baseline
To assess the preliminary antitumour activity of AZD5305 in combination with NHA.
Measured: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Number of patients with ≥ 90% prostate-specific antigen (PSA) decrease from baseline
To assess the preliminary antitumour activity of AZD5305 in combination with NHA.
Measured: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Part B: Number of patients with undetectable PSA (< 0.2 ng/mL)
To assess the preliminary antitumour activity of AZD5305 in combination with NHA.
Measured: 3, 6, 9 and 12 months
PSA Progression-free survival
To assess the preliminary antitumour activity of AZD5305 in combination with NHA.
Measured: 6, 12, 18, 24 and 30 months
AUC of Enzalutamide
To characterize the PK (AUC) of Enzalutamide in plasma at steady state when given orally in combination with AZD5305
Measured: At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
Cmax of Enzalutamide
To characterize the PK (Cmax) of Enzalutamide in plasma at steady state when given orally in combination with AZD5305
Measured: At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
tmax of Enzalutamide
To characterize the PK (tmax) of Enzalutamide in plasma at steady state when given orally in combination with AZD5305
Measured: At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
AUC of Apalutamide
To characterize the PK (AUC) of Apalutamide in plasma at steady state when given orally in combination with AZD5305
Measured: At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
Cmax of Apalutamide
To characterize the PK (Cmax) of Apalutamide in plasma at steady state when given orally in combination with AZD5305
Measured: At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
tmax of Apalutamide
To characterize the PK (tmax) of Apalutamide in plasma at steady state when given orally in combination with AZD5305
Measured: At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
Part B: Homologous recombination repair gene mutation (HRRRm)
To investigate HRRm (including BRCA1/2) and their relationship with clinical response
Measured: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2022
- Study start2 Jun 2022
- Primary completion11 Apr 2031 (estimated)
- Study completion11 Apr 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Prostate CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 174 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bayer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05367440
- Sponsor's protocol ID
- D9720C00003
- Other IDs
- 2023-508536-64-00, 2021-006289-19, 2023
- Acronym
- PETRANHA
- Status last verified
- Aug 2026
- First submitted
- 19 Apr 2022
- Last updated
- 26 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests 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.
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05367440
- Acronym / sponsor ID
- PETRANHA / D9720C00003
- Conditions
- Metastatic Prostate Cancer
- Keywords
- PETRANHA, AZD5305, New Hormonal Agents
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 174 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Bayer
- Study start
- 2 Jun 2022 (actual)
- Primary completion
- 11 Apr 2031 (estimated)
- Study completion
- 11 Apr 2031 (estimated)
- First posted
- 10 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will 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.
Detailed description
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 4 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 4 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 783 patients will be enrolled and screened to ensure the required number of evaluable patients in each part and arm are enrolled. For Part A, 356 patients may be screened to obtain up to approximately 308 patients that can be assigned to study treatments across all study arms (1 to 4). For Part B dose expansion cohorts, up to 427 patients may be screened to obtain up to approximately 360 patients that can be assigned to study treatments across all study arms (1 to 4).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (AZD5305 in combination with enzalutamide) | Experimental | Drug: AZD5305, Drug: EnzalutamidePatients 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. |
| Arm 2 (AZD5305 in combination with abiraterone acetate) | Experimental | Drug: AZD5305, Drug: Abiraterone AcetatePatients 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. |
| Arm 3 (AZD5305 in combination with darolutamide) | Experimental | Drug: AZD5305, Drug: DarolutamidePatients 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. |
| Arm 4 (AZD5305 in combination with apalutamide) | Experimental | Drug: ApalutamidePatients 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. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age ≥ 18 at the time of screening.
- Histologically confirmed diagnosis of metastatic prostate cancer.
- Candidate for treatment with enzalutamide, abiraterone acetate, darolutamide or apalutamide with documented current evidence of metastatic prostate cancer.
- Surgically or medically castrated.
- Adequate organ and marrow function.
Key exclusion criteria (34 listed)
- 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 PARPi, 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:
- Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD5305Patients will receive an oral dose of AZD5305 once daily | Drug | Arm 1 (AZD5305 in combination with enzalutamide), Arm 2 (AZD5305 in combination with abiraterone acetate), Arm 3 (AZD5305 in combination with darolutamide) |
| EnzalutamideAlso: XtandiPatients will receive an oral dose of Enzalutamide once daily | Drug | Arm 1 (AZD5305 in combination with enzalutamide) |
| Abiraterone AcetateAlso: ZytigaPatients will receive an oral dose of Abiraterone Acetate once daily | Drug | Arm 2 (AZD5305 in combination with abiraterone acetate) |
| DarolutamideAlso: NubeqaPatients will receive an oral dose of Darolutamide twice daily | Drug | Arm 3 (AZD5305 in combination with darolutamide) |
| ApalutamideAlso: ErleadaPatients will receive an oral dose of Apalutamide once daily | Drug | Arm 4 (AZD5305 in combination with apalutamide) |
Primary outcome
Number of patients with Adverse Events and Serious Adverse Events
Time frame: Up to post treatment follow-up (28 days after last dose) [assessed up to 2.3 years]
Number of patients with adverse events and with serious adverse events including abnormal clinical observations, abnormal ECG parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline will be assessed.
Part A: Number of patients with Dose Limiting Toxicities (DLTs)
Time frame: For Arm 1: 35 days, For Arm 2 and 3: 28 days
To assess the safety and tolerability of AZD5305 when given in combination with NHA.
22 secondary outcomes
Area Under the concentration Curve (AUC) of AZD5305
Time frame: At the end of Cycle 0 (Cycle 0 is of 7 days)
Maximum plasma concentration (Cmax) of AZD5305
Time frame: At the end of Cycle 0 (Cycle 0 is of 7 days)
Time to maximum concentration (tmax) of AZD5305
Time frame: At the end of Cycle 0 (Cycle 0 is of 7 days)
AUC of AZD5305
Time frame: Arm 1: At Cycle 1 Day 1, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8, and Cycle 3 Day 1; Arm 2 and 3: At Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Each Cycle is of 28 days)
Cmax of AZD5305
Time frame: Arm 1: At Cycle 1 Day 1, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8, and Cycle 3 Day 1; Arm 2 and 3: At Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Each Cycle is of 28 days)
tmax of AZD5305
Time frame: Arm 1: At Cycle 1 Day 1, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8, and Cycle 3 Day 1; Arm 2 and 3: At Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Each Cycle is of 28 days)
Objective response rate (ORR)
Time frame: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Duration of response (DoR)
Time frame: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Time to response (TTR)
Time frame: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Radiographic progression-free survival (rPFS)
Time frame: From Screening (Day -28), 12 months, 24 months and up to confirmed disease progression [assessed up to 2.3 years]
Percentage change in tumour size
Time frame: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Number of patients with ≥ 50% prostate-specific antigen (PSA) decrease from baseline
Time frame: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Number of patients with ≥ 90% prostate-specific antigen (PSA) decrease from baseline
Time frame: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Part B: Number of patients with undetectable PSA (< 0.2 ng/mL)
Time frame: 3, 6, 9 and 12 months
PSA Progression-free survival
Time frame: 6, 12, 18, 24 and 30 months
AUC of Enzalutamide
Time frame: At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
Cmax of Enzalutamide
Time frame: At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
tmax of Enzalutamide
Time frame: At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
AUC of Apalutamide
Time frame: At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
Cmax of Apalutamide
Time frame: At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
tmax of Apalutamide
Time frame: At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
Part B: Homologous recombination repair gene mutation (HRRRm)
Time frame: From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2026.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
20 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZD5305, Enzalutamide and Abiraterone Acetate in people with Metastatic Prostate Cancer, run by AstraZeneca at 20 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Australia, Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with Adverse Events and Serious Adverse Events (time frame: Up to post treatment follow-up (28 days after last dose) [assessed up to 2.3 years]). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026; AzTrials last refreshed its copy on 6 Nov 2026.