AZD5305 for Prostate Cancer

(EvoPAR-PR01 Trial)

Recruiting in Palo Alto (17 mi)

+304 other locations

Overseen by Arun Azad

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Must be taking: GnRH analogues

Disqualifiers: MDS/AML, Bleeding predisposition, Severe cytopenia, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called Saruparib combined with hormone treatment in adults with prostate cancer that has spread but still responds to hormones. The drug aims to stop cancer cells from repairing themselves, potentially slowing down the disease.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have had prior anticancer pharmacotherapy or surgery for metastatic prostate cancer, with some exceptions. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug AZD5305 for prostate cancer?

Research shows that enzalutamide, a similar drug used in combination with androgen-deprivation therapy, significantly improved survival outcomes in prostate cancer patients. This suggests that AZD5305, which may work in a similar way, could also be effective. ^{1 2 3 4 5}

What safety data exists for AZD5305 or related treatments in prostate cancer?

The ARAMIS trial showed that darolutamide, a related treatment, had a favorable safety profile in patients with non-metastatic castration-resistant prostate cancer, meaning it was generally well-tolerated with manageable side effects. ^{6 7 8 9 10}

What makes the drug AZD5305 unique for prostate cancer treatment?

AZD5305, also known as Saruparib, is a novel treatment for prostate cancer that may offer a different mechanism of action compared to traditional therapies like chemotherapy or androgen receptor inhibitors. While specific details about AZD5305's mechanism are not provided, it is distinct from existing treatments such as docetaxel-based chemotherapy and newer options like enzalutamide, which target the androgen receptor pathway. ^{11 12 13 14 15}

Research Team

Arun Azad

Principal Investigator

Peter MacCallum Cancer Centre, Australia

Kim Nguyen Chi, MD

Principal Investigator

BC Cancer, Canada

Eligibility Criteria

This trial is for men over 18 with metastatic castration-sensitive prostate cancer, showing at least one bone or soft tissue lesion. They must have started hormone therapy recently and be in good physical condition. Men with certain types of aggressive cancer cells, previous severe blood disorders, or prior treatment for metastatic cancer are excluded.

Inclusion Criteria

My cancer has spread, and I have at least one bone or soft tissue lesion that can be monitored with scans.

As a participant, you must abstain from fathering children or donating sperm for the duration of the study intervention and 6 months following its completion.

My cancer has a specific genetic change confirmed by tests.

Exclusion Criteria

I have not received blood products or growth factors in the last 14 days.

I have had treatment or surgery for advanced prostate cancer, with some exceptions.

I cannot take pills due to severe nausea, vomiting, or other serious gut issues.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Saruparib (AZD5305) or placebo in combination with physician's choice new hormonal agents until disease progression or treatment discontinuation

up to approximately 50 months

Follow-up

Participants are monitored for survival and other outcomes after treatment

up to approximately 90 months

Treatment Details

Interventions

• Abiraterone Acetate (Hormone Therapy)
• AZD5305 (Hormone Therapy)
• Darolutamide (Hormone Therapy)
• Enzalutamide (Hormone Therapy)
• Placebo (Hormone Therapy)

Trial Overview The study aims to see if AZD5305 combined with a hormonal agent chosen by the physician works better than a placebo combined with the same hormonal agent. The main goal is to check if this combination can slow down the progression of prostate cancer as seen on imaging tests.

Participant Groups

Group I: Arm 1: Saruparib (AZD5305) + Physician's Choice NHA Experimental Treatment 4 Interventions

Saruparib (AZD5305) + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)

Group II: Arm 2: Placebo + Physician's Choice NHA Placebo Group 4 Interventions

Placebo + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide)

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

Enzalutamide significantly improved radiographic progression-free survival (rPFS) in men with chemotherapy-naïve metastatic castration-resistant prostate cancer across various disease subgroups, including nonvisceral and visceral disease, as well as low- and high-volume bone disease.

The treatment was well tolerated, showing clinically significant benefits in overall survival (OS) for most subgroups, although the results were less definitive for patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer. Evans, CP., Higano, CS., Keane, T., et al.[2022]

Rucaparib, a PARP inhibitor, has been granted accelerated approval for treating men with metastatic castration-resistant prostate cancer (mCRPC) who have BRCA1 or BRCA2 mutations, based on safety data from clinical trials involving 193 participants.

Common treatment-emergent adverse events (TEAEs) include gastrointestinal issues, fatigue, and anemia, with most being self-limiting; effective management of these TEAEs is crucial to maximize the benefits of rucaparib treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for Management of Treatment-Emergent Adverse Events During Rucaparib Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. Labadie, BW., Morris, DS., Bryce, AH., et al.[2022]

In a large registry study involving 1976 patients with metastatic castration-resistant prostate cancer, sipuleucel-T immunotherapy demonstrated a median overall survival of 30.7 months, indicating its potential effectiveness in prolonging life for this patient group.

The treatment was associated with a low incidence of serious adverse events (3.9%) and cerebrovascular events (2.8%), suggesting that sipuleucel-T is a relatively safe option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer. Higano, CS., Armstrong, AJ., Sartor, AO., et al.[2021]

In the ARAMIS trial, darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% compared to placebo in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

The overall survival benefit of darolutamide was consistent across patients with varying numbers of comorbidities and concomitant medications, with similar rates of treatment-emergent adverse events compared to placebo, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety outcomes of darolutamide in patients with non-metastatic castration-resistant prostate cancer with comorbidities and concomitant medications from the randomised phase 3 ARAMIS trial. Fizazi, K., Shore, ND., Smith, M., et al.[2023]

The TALAPRO-3 study is a phase III clinical trial designed to evaluate the effectiveness of combining talazoparib, a poly(ADP-ribose) polymerase inhibitor, with enzalutamide in patients with metastatic castration-sensitive prostate cancer (mCSPC) who have homologous recombination repair (HRR) gene alterations.

The primary goal of the study is to determine if this combination therapy can improve radiographic progression-free survival (rPFS) compared to enzalutamide alone, potentially offering a new treatment strategy for patients with specific genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TALAPRO-3 clinical trial protocol: phase III study of talazoparib plus enzalutamide in metastatic castration-sensitive prostate cancer. Agarwal, N., Saad, F., Azad, AA., et al.[2023]

The TALAPRO-2 study is a phase III clinical trial designed to evaluate the effectiveness of talazoparib combined with enzalutamide compared to placebo with enzalutamide in treating metastatic castration-resistant prostate cancer (mCRPC).

The study aims to determine if this combination therapy can significantly improve radiographic progression-free survival (rPFS) in patients with or without DNA damage response (DDR) alterations, potentially enhancing treatment outcomes for mCRPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: TALAPRO-2 phase III study design. Agarwal, N., Azad, A., Shore, ND., et al.[2022]

Enzalutamide, when combined with a Twist-targeting immunotherapy, significantly improved overall survival in a mouse model of castration-resistant prostate cancer (CRPC), extending survival from 10.3 weeks to 27.5 weeks.

The study found that enzalutamide did not impair the immune response generated by the Twist vaccine, suggesting that this combination therapy could be a safe and effective strategy for treating advanced-stage prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with a second-generation androgen receptor antagonist and a metastasis vaccine improves survival in a spontaneous prostate cancer model. Ardiani, A., Farsaci, B., Rogers, CJ., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Eyeing Enzalutamide for Hormone-Sensitive Prostate Cancer. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Stratifying prostate patients for olaparib. [2015]

3. Switzerland pubmed.ncbi.nlm.nih.gov

The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Deep Prostate-specific Antigen Response following Addition of Apalutamide to Ongoing Androgen Deprivation Therapy and Long-term Clinical Benefit in SPARTAN. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Proof-of-Concept with PROTACs in Prostate Cancer. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Guidelines for Management of Treatment-Emergent Adverse Events During Rucaparib Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety outcomes of darolutamide in patients with non-metastatic castration-resistant prostate cancer with comorbidities and concomitant medications from the randomised phase 3 ARAMIS trial. [2023]

9. England pubmed.ncbi.nlm.nih.gov

TALAPRO-3 clinical trial protocol: phase III study of talazoparib plus enzalutamide in metastatic castration-sensitive prostate cancer. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: TALAPRO-2 phase III study design. [2022]

11. England pubmed.ncbi.nlm.nih.gov

A phase II trial of the Src-kinase inhibitor AZD0530 in patients with advanced castration-resistant prostate cancer: a California Cancer Consortium study. [2021]

12. United Arab Emirates pubmed.ncbi.nlm.nih.gov

New perspectives in the therapy of castration resistant prostate cancer. [2019]

13. China pubmed.ncbi.nlm.nih.gov

Enzalutamide (formerly MDV3100) as a new therapeutic option for men with metastatic castration-resistant prostate cancer. [2021]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Combination AZD5363 with Enzalutamide Significantly Delays Enzalutamide-resistant Prostate Cancer in Preclinical Models. [2022]

15. United States pubmed.ncbi.nlm.nih.gov

Combination therapy with a second-generation androgen receptor antagonist and a metastasis vaccine improves survival in a spontaneous prostate cancer model. [2021]