EVOPAR

Trial Info

Status: Open

Specialty: Prostate

Date Opened: 30/04/2024

Planned Close Date: 31/05/2026

Sponsor: AstraZeneca

Principal Investigator: Dr Omi Parikh

Study Title: A Randomized, 2-cohort, Double-blind, Placebo-controlled, Phase III Study of AZD5305 in Combination with Physician’s Choice New Hormonal Agents in Patients with HRRm and non-HRRm Metastatic Castration-Sensitive Prostate Cancer (EvoPAR-Prostate01)

Trial Description

This is a Phase III double-blind, randomised, placebo-controlled, adaptive design study, to assess whether the addition of AZD5305 to physician’s choice NHA improves treatment outcomes of patients in the setting of mCSPC. A schema summarising the key elements of the study design is shown in Figure 1.

A total of 1200 participants will be randomised (in a 1:1 ratio) to receive either AZD5305 (600 participants) or matching placebo (600 participants), in combination with physician’s choice of NHA (abiraterone, darolutamide, or enzalutamide) on a background of ADT.

The randomisation scheme will be stratified on the following factors:

• HRRm/BRCAm status: Prospective FFPE tumour tissue and peripheral blood ctDNA testing will be needed from participants and used for stratification;

• Volume of disease per investigator (high vs. low) according to CHAARTED criteria*

o *High volume is defined as the presence of visceral metastases and / or ≥ 4 bone metastases with ≥ 1 metastasis beyond the pelvis and vertebral column;

• Physician’s choice NHA:

o Abiraterone

o Darolutamide

o Enzalutamide.

The study will have an adaptive design, with two interim analyses (interim analysis 1 for futility and interim analysis 2 for sample size re-estimation and adaptive enrichment).

Prior to randomization, an FFPE tumour tissue sample from the participant as well as a peripheral blood sample for ctDNA will need to be submitted for prospective testing of HRRm/BRCAm status. The participant will be stratified based on the results from those tests, and treatment on study can be initiated only after test results are available. Participants with a tissue test result of ‘unknown’ will be eligible, up until the moment a cap on the ‘unknown’ stratum is reached. Treatment with ADT can be commenced whilst awaiting biomarker test results, so long as participants are randomized within 4 months.

Response evaluation criteria in solid tumours (RECIST) tumour assessments (computed tomography/magnetic resonance imaging) and Prostate Cancer Working Group-3 (PCWG3) assessments (bone scan) will be performed in cycle 3, 5 and every 16 weeks (± 14 days) thereafter until investigator-assessed disease progression by RECIST 1.1 or PCWG-3 bone progression criteria.

It is anticipated that the first participant will be enrolled in Quarter 3, 2023. The last subject last visit date is predicted to occur in October 2030.

Participants will receive study intervention until investigator-assessed

Inclusion Criteria

1. Castration-sensitive, histologically documented prostate adenocarcinoma.

2. De novo or recurrent, metastatic disease documented prior to randomisation by clear evidence of ≥ 1 bone lesion (defined as ≥ 1 lesion with positive uptake on technetium-99m bone scan) and/or ≥ 1 soft tissue lesion (measurable and/or non-measurable) identified via CT and/or MRI that is suitable for repeated assessments.

3. Participants is receiving androgen deprivation therapy (ADT) either with an GnRH analogue or has undergone bilateral orchiectomy starting ≥ 14 days and < 4 months prior to randomisation, and with no evidence of disease progression since initiation of therapy.

4. ECOG performance status of 0 or 1.

5. Minimum life expectancy 6 months.

6. Provision of FFPE tumour tissue sample of sufficient volume and quality as specified in the Laboratory Manual to assess HRRm/BRCAm status. Sample requirements: FFPE block or 20+ unstained sections (4-5 micron thickness) with minimum 20% tumour content.

7. Adequate organ and marrow function.

Exclusion Criteria

1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled diseases or active uncontrolled infections) which, in the investigator’s opinion, make it undesirable for the participant to participate in the study or would jeopardise compliance with the protocol.

2. History of another primary malignancy, with the following exceptions:

• Adequately resected non-melanoma skin cancer

• Curatively treated in situ disease

• Malignancy treated with curative intent ≥ 5 years before the first dose of study intervention, and with no known active disease during the intervening time period.

3. Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to randomisation.

4. Participants with mean resting corrected QT interval (QTcF) > 450 milliseconds, family history of QT abnormalities, or clinically important abnormalities in heart rhythm, conduction or morphology of resting ECG that are not adequately controlled.

5. Other cardiovascular diseases, including but not limited to: symptomatic heart failure, uncontrolled hypertension, unstable angina pectoris, presence of clinically significant valvular heart disease and history of acute coronary syndrome within 6 months.

Contacts

Research Nurse: Catherine Walmsley (x8475) Catherine.Walmsley@lthtr.nhs.uk

Administrator: Aaisha Khan (x8475)

Link to EDGE

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