Home › Trials › NCT05367440

Combining AZD5305 with new hormonal agents for metastatic prostate cancer

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)

Phase1; Phase2 Interventional AstraZeneca · NCT05367440

This study is testing if a new drug called AZD5305, when combined with other hormonal treatments, can help people with advanced prostate cancer feel better and manage their disease.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment190 (estimated)
Ages18 Years to 130 Years
SexMale
SponsorAstraZeneca Industry-sponsored
Drugs / interventionschemotherapy, radiation, prednisone
Locations27 sites (San Diego, California and 26 other locations)
Trial IDNCT05367440 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AZD5305 in combination with new hormonal agents in patients with metastatic prostate cancer. It consists of two parts: Part A focuses on dose escalation with patients having either metastatic castration-resistant or castration-sensitive prostate cancer, while Part B involves dose expansion specifically for metastatic castration-sensitive prostate cancer. Approximately 783 patients will be screened to ensure adequate enrollment across various treatment arms, with treatment continuing until disease progression or other discontinuation reasons occur.

Who should consider this trial

Good fit: Ideal candidates include adult males with histologically confirmed metastatic prostate cancer who are candidates for treatment with specific hormonal agents.

Not a fit: Patients who do not have metastatic prostate cancer or those who are not candidates for the hormonal agents being tested may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with metastatic prostate cancer.

How similar studies have performed: Other studies have shown promise with similar combinations of hormonal agents and novel treatments, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
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, darolutamide or apalutamide 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

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).

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:

  1. Strong and moderate CYP3A4 inducers/inhibitors (applies for all arms)
  2. For Arm 1 (enzalutamide) patients: Strong CYP2C8 inhibitors
  3. 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:

  1. 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.
  2. 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.
  3. 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.

Where this trial is running

San Diego, California and 26 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Prostate CancerPETRANHAAZD5305New Hormonal Agents
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.