AZD5305 + Hormonal Therapy for Prostate Cancer

(PETRANHA Trial)

Recruiting in Palo Alto (17 mi)

+18 other locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: AstraZeneca

Must be taking: New hormonal agents

Must not be taking: PARPi, Platinum, Immuno-oncology, others

Disqualifiers: Severe pancytopenia, Brain metastases, Cardiovascular diseases, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, AZD5305, combined with hormone treatments in patients with advanced prostate cancer. It aims to see if this combination is safe and effective. The study focuses on patients whose cancer either continues to grow despite hormone therapy or is still responsive to it.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including strong and moderate CYP3A4 inducers/inhibitors, and specific drugs depending on the treatment arm you are in. You should discuss your current medications with the study team to see if any need to be stopped.

What data supports the effectiveness of the drug AZD5305 + Hormonal Therapy for Prostate Cancer?

Research shows that abiraterone acetate, a component of the treatment, significantly improves survival and delays disease progression in patients with metastatic castration-resistant prostate cancer. Additionally, combining abiraterone with enzalutamide, another component, further enhances survival outcomes when used with androgen deprivation therapy. ^{1 2 3 4 5}

What safety data exists for enzalutamide and abiraterone acetate in prostate cancer treatment?

Enzalutamide and abiraterone acetate, used for treating prostate cancer, have been studied for their safety. They are generally well-tolerated, but some patients may experience fatigue and changes in quality of life. ^{2 6 7 8 9}

How is the drug AZD5305 + Hormonal Therapy for Prostate Cancer different from other treatments?

This treatment combines AZD5305, a novel drug, with existing hormonal therapies like abiraterone acetate and enzalutamide, which are used to treat prostate cancer by blocking hormones that fuel cancer growth. The unique aspect is the inclusion of AZD5305, which may offer a new mechanism of action or enhanced effectiveness compared to standard treatments. ^{1 2 5 7 10}

Research Team

Eligibility Criteria

Men over 18 with metastatic prostate cancer who are candidates for treatment with enzalutamide, abiraterone acetate, or darolutamide. They must be castrated (surgically or medically), have good organ and marrow function, an ECOG Performance Status of 0-1, a life expectancy of at least 16 weeks, and agree to use contraception if necessary. Not eligible if they've had certain prior treatments like PARP inhibitors in the mCSPC setting or strong CYP3A4 inducers.

Inclusion Criteria

My organs and bone marrow are working well.

Life expectancy ≥ 16 weeks.

I am eligible for specific prostate cancer treatments and my cancer has spread.

Exclusion Criteria

I have not had treatments like PARP inhibitors or chemotherapy for my prostate cancer.

I have not used new hormonal agents for my condition.

I haven't had certain treatments or vaccines recently and don't have severe health issues.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment - Part A

Dose escalation cohorts evaluating the safety, tolerability, and preliminary efficacy of AZD5305 in combination with a specific new hormonal agent

35 days for Arm 1, 28 days for Arms 2 and 3

Treatment - Part B

Dose expansion cohorts investigating the preliminary efficacy and building on the safety data for the combination of AZD5305 with a specific NHA

Until disease progression or other discontinuation criteria

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days after last dose

Treatment Details

Interventions

• Abiraterone Acetate (Androgen Receptor Antagonist)
• AZD5305 (Other)
• Darolutamide (Androgen Receptor Antagonist)
• Enzalutamide (Androgen Receptor Antagonist)

Trial Overview The trial is testing AZD5305 combined with new hormonal agents (NHAs) such as enzalutamide, abiraterone acetate, or darolutamide in men with metastatic prostate cancer. It aims to assess safety and how well the body handles the drug combination while also looking at early signs of effectiveness.

Participant Groups

Group I: Arm 4 (AZD5305 in combination with apalutamide) Experimental Treatment 1 Intervention

Patients will receive an oral dose of AZD5305 and Apalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Group II: Arm 3 (AZD5305 in combination with darolutamide) Experimental Treatment 2 Interventions

Patients will receive an oral dose of AZD5305 once daily and Darolutamide twice daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Group III: Arm 2 (AZD5305 in combination with abiraterone acetate) Experimental Treatment 2 Interventions

Patients will receive an oral dose of AZD5305 and Abiraterone Acetate once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Group IV: Arm 1 (AZD5305 in combination with enzalutamide) Experimental Treatment 2 Interventions

Patients will receive an oral dose of AZD5305 and Enzalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Abiraterone Acetate is already approved in Canada, Japan for the following indications:

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic castration-sensitive prostate cancer

Approved in Japan as Zytiga for:

• Prostate cancer

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

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Findings from Research

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

In a study involving 1919 patients with metastatic prostate cancer, the addition of abiraterone acetate to standard androgen deprivation therapy significantly improved overall survival, with a median survival of 76.6 months compared to 45.7 months for standard care alone.

Combining both abiraterone and enzalutamide did not provide additional survival benefits over abiraterone alone, and it was associated with higher rates of severe side effects, suggesting that this combination should be avoided in long-term treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

In a study of 3,398 patients with metastatic castration-resistant prostate cancer, those initiated on abiraterone acetate (AA) had a significantly longer duration of treatment compared to those initiated on enzalutamide (ENZ), with a median duration of 18.3 months for AA versus 14.2 months for ENZ.

Patients on AA also experienced fewer treatment discontinuations at various time points, indicating that AA may provide a more sustained treatment option for managing prostate cancer compared to ENZ.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of Treatment in Prostate Cancer Patients Treated with Abiraterone Acetate or Enzalutamide. Pilon, D., Behl, AS., Ellis, LA., et al.[2023]

A study involving 32 healthy male subjects demonstrated that the test product (abiraterone acetate tablet) is bioequivalent to the reference product ZYTIGA® in terms of pharmacokinetics, with both products showing similar maximum concentration (Cmax) and area under the curve (AUC) values within the acceptable range.

The research confirmed significant intra-subject variability in the pharmacokinetics of abiraterone, indicating that individual responses to the drug can vary widely, which is important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Wang, C., Hu, C., Gao, D., et al.[2022]

In a study of 170 men with metastatic castration-resistant prostate cancer, treatment with abiraterone acetate plus prednisone (AAP) resulted in significantly less fatigue compared to enzalutamide, with a clinically meaningful difference of 3.4 points on the fatigue scale.

However, AAP was associated with a greater increase in glycated hemoglobin (HbA1c) levels and a higher incidence of type 2 diabetes, indicating potential metabolic risks compared to enzalutamide, which did not lead to any cases of diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatigue, health-related quality-of-life and metabolic changes in men treated with enzalutamide or abiraterone acetate plus prednisone for metastatic castration-resistant prostate cancer: A randomised clinical trial (HEAT). Ternov, KK., Sønksen, J., Fode, M., et al.[2022]

In a study of 211 patients with metastatic castration-resistant prostate cancer, abiraterone acetate plus prednisone (AAP) showed significantly better outcomes than enzalutamide (ENZ) in terms of cognitive function and fatigue over the first three months of treatment.

Patients receiving AAP reported less perceived cognitive impairment and lower levels of fatigue compared to those on ENZ, indicating that AAP may be a more favorable option for managing these patient-reported outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of abiraterone acetate plus prednisone or enzalutamide on fatigue and cognition in patients with metastatic castration-resistant prostate cancer: initial results from the observational AQUARiUS study. Thiery-Vuillemin, A., Hvid Poulsen, M., Lagneau, E., et al.[2021]

In a study of 100 patients with metastatic castration-resistant prostate cancer, those treated with enzalutamide (ENZA) reported significantly more fatigue and neurocognitive issues compared to those treated with abiraterone acetate plus prednisone (AA+P).

While both treatments had similar rates of severe adverse events, ENZA was associated with unique neuropsychiatric side effects such as memory impairment and confusion, indicating a need for careful monitoring of cognitive function in patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Real-world Study of Enzalutamide and Abiraterone Acetate With Prednisone Tolerability (REAAcT). Shore, ND., Saltzstein, D., Sieber, P., et al.[2021]

Enzalutamide showed a higher prostate-specific antigen response compared to abiraterone in patients with metastatic castration-resistant prostate cancer, indicating greater efficacy in treatment.

However, enzalutamide was associated with a significantly higher rate of adverse events, particularly fatigue, compared to abiraterone, highlighting a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the clinical efficacy and safety of abiraterone and enzalutamide in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis. Wang, X., Yang, H., Hu, X., et al.[2021]

Abiraterone acetate (Zytiga®) is an effective antiandrogen for prostate cancer but has poor oral bioavailability (<10%) and requires patients to fast around its administration due to a significant food effect (5-10-fold increase in absorption).

The review highlights the need for improved oral formulation strategies to enhance solubility and bioavailability of abiraterone acetate, aiming to reduce the required dose and eliminate the food effect, which could lead to better patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. Schultz, HB., Meola, TR., Thomas, N., et al.[2020]

References

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

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. [2023]

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

The Effect of Time to Castration Resistance on Outcomes With Abiraterone and Enzalutamide in Metastatic Prostate Cancer. [2021]

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

Duration of Treatment in Prostate Cancer Patients Treated with Abiraterone Acetate or Enzalutamide. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Fatigue, health-related quality-of-life and metabolic changes in men treated with enzalutamide or abiraterone acetate plus prednisone for metastatic castration-resistant prostate cancer: A randomised clinical trial (HEAT). [2022]

7. England pubmed.ncbi.nlm.nih.gov

Impact of abiraterone acetate plus prednisone or enzalutamide on fatigue and cognition in patients with metastatic castration-resistant prostate cancer: initial results from the observational AQUARiUS study. [2021]

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

Results of a Real-world Study of Enzalutamide and Abiraterone Acetate With Prednisone Tolerability (REAAcT). [2021]

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

Comparing the clinical efficacy and safety of abiraterone and enzalutamide in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. [2020]