AZD5305 vs Placebo in Men with Metastatic Castration-Sensitive Prostate Cancer Receiving Physician's Choice New Hormonal Agents.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Jun 2024 → ongoing

Decision date (initial)

2024-03-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy

To demonstrate superiority of AZD5305 + physician's choice NHA relative to placebo + physician's choice NHA by assessment of radiographic progression-free survival (rPFS)in participants with mCSPC in the BRCAm subpopulation within the HRRmcohort and the non-HRRm cohort.

Secondary objectives 1

1. To demonstrate superiority of AZD5305 + physician's choice NHA relative to placebo + physician's choice NHA by assessment of overall survival (OS) in participants with mCSPC in the BRCAm subpopulation within the HRRm cohort, in the HRRm cohort, and the non-HRRm cohort.

Conditions and MedDRA coding

Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-003447-PIP01-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male ≥ 18 years of age.
2. Histologically documented prostate adenocarcinoma which is de novo or recurrent and castration-sensitive. Participants with pathologic features of small cell, neuroendocrine, sarcomatoid, spindle cell, or signet cell histology are not eligible.
3. Metastatic disease as documented by the investigator prior to randomisation, with clear evidence of ≥ 1 bone lesion and/or ≥ 1 soft tissue lesion that is suitable for repeated assessment with CT and/or MRI.
4. Participant is receiving ADT with a GnRH analogue or has undergone bilateral orchiectomy starting ≥ 14 days and < 4 months prior to randomisation.
5. ECOG performance status of 0 or 1 with no deterioration over the 2 weeks prior to randomisation.
6. Provision of FFPE tumour tissue sample and blood sample (for ctDNA).
7. Confirmed HRRm status by central tumour tissue and/or ctDNA test is required to determine cohort eligibility.
8. Adequate organ and bone marrow function as described in study protocol.
9. Participants must not father children or donate sperm from signing ICF, during the study intervention and for 6 months after the last dose of study intervention.
10. Participants must use a condom from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners.

Exclusion criteria 12

1. Participants with a history of MDS/AML or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). In case there is no clinical MDS/AML suspicion, no specific screening for MDS/AML (by BM/bone biopsy) is required.
2. Prior treatment within 14 days with blood product support or growth factor support.
3. Participants who are unevaluable for both bone and soft tissue progression.
4. Participants with any known predisposition to bleeding.
5. Any history of persisting (> 2 weeks) severe cytopenia.
6. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5305 and/or the assigned NHA.
7. History of another primary malignancy, with the following exceptions: a) Adequately resected non-melanoma skin cancer. b) Curatively treated in situ disease. c) Malignancy treated with curative intent ≥ 3 years before the first dose of study intervention, and with no known active disease during the intervening time period.
8. Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy.
9. Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
10. Cardiac criteria, including history of arrythmia and cardiovascular disease.
11. Any prior anticancer pharmacotherapy or surgery for metastatic prostate cancer, with the following exceptions: a) ≤ 4 months ADT for metastatic disease (per inclusion criterion 4). b) Radiation therapy (for example radiation therapy to the prostate for participants with low volume metastatic disease or palliative radiation therapy to treat symptoms resulting from metastatic disease). Radiation therapy needs to have been completed > 4 weeks prior to randomisation for wide field radiation therapy and > 2 weeks for limited field radiation therapy. Participants should have fully recovered from any clinically significant adverse events. c) Surgical therapy to treat symptoms from metastatic disease if it was completed at least 4 weeks prior to first day of dosing and participant fully recovered from any clinically significant AEs.
12. Patients in whom the standard of care is judged by the investigator to be docetaxelin combination with darolutamide.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Radiographic progression-free survival, defined as the time from randomisation to radiographic progression, as assessed by the investigator per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone) or death due to any cause.

Secondary endpoints 6

1. Overall Survival, defined as the time from the date of randomisation until death due to any cause.
2. Time to Second Progression or Death (PFS2), defined as the time from randomisation to the earliest progression after initiation of first subsequent treatment following the initial investigator-assessed progression or death.
3. Time to First Subsequent Therapy or Death (TFST), defined as the time from randomisation to the start date of the first subsequent anticancer therapy after discontinuation of randomised treatment, or death due to any cause.
4. Symptomatic Skeletal Event-free Survival.
5. Time to Castration-Resistance (TTCR), defined as the time from randomisation to the first castration-resistant event.
6. Clinical Outcome Assessments, including TTPP, TTDUS, TTDF, TTDPF, and HRQoL.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

11 EU/EEA countries · 102 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 149 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications