Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer

Trial number:
NCT05367440
Trial phase:
1, 2
Study type:
Targeted therapy, Hormonal therapy
Overall status:
Recruiting

Study start date

June, 2022

Scientific 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).

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

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. Patients with Metastatic Castrate Resistant Prostate Cancer (mCRPC) or Metastatic Hormone Sensitive Prostate Cancer (mHSPC). 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.

Concomitant use of medications or herbal supplements that may involve severe drug-drug interactions with the study treatment.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 shorter) 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. Any previous treatment with a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor, Lu-PSMA, platinum chemotherapy, docetaxel (for mHSPC patients). Major surgery within 4 weeks prior to the first dose of study treatment. Radiotherapy within 4 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. 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.

Study design

Primary purpose: Treatment, Allocation: Non-Randomized, Intervention model: Parallel Assignment, Masking: None (Open Label),

Conditions

Metastatic Prostate Cancer

Other study ID numbers

D9720C00003; 2021-006289-19

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