Capivasertib + Abiraterone for Prostate Cancer

(SNARE Trial)

Recruiting at 4 trial locations

Overseen By Ryan P Kopp, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must be taking: Androgen deprivation drugs

Must not be taking: Anti-androgens, Chemotherapy

Disqualifiers: Uncontrolled diseases, Active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot take certain medications like potent inhibitors or inducers of CYP3A4, drugs that prolong the QT interval, or any medication that may interfere with abiraterone. It's best to discuss your current medications with the trial team to see if they are allowed.

What data supports the idea that Capivasertib + Abiraterone for Prostate Cancer is an effective drug?

The available research shows that Abiraterone, when used with prednisone, significantly improves survival in patients with advanced prostate cancer. It helps delay the progression of the disease and increases the time patients live without the cancer getting worse. In one study, Abiraterone was shown to extend survival by about four months in patients who had already received chemotherapy. This makes it a strong option for treating prostate cancer, especially when compared to a placebo, which is a treatment with no active drug. ^{1 2 3 4 5}

What safety data is available for Capivasertib and Abiraterone in prostate cancer treatment?

Abiraterone acetate, marketed as Zytiga, is used in combination with prednisone or prednisolone for treating metastatic castration-resistant prostate cancer (CRPC). Clinical trials have shown it significantly prolongs overall survival and progression-free survival. The safety profile is generally acceptable, with common side effects including hypokalaemia, hypertension, fluid retention, cardiac events, and hepatotoxicity. The incidences of severe adverse events were relatively low in phase III studies. There is no specific safety data provided for Capivasertib in the provided research. ^{1 2 6 7 8}

Is the drug Capivasertib + Abiraterone a promising treatment for prostate cancer?

Yes, the drug Capivasertib + Abiraterone is promising for prostate cancer. Abiraterone has been shown to significantly improve survival and delay disease progression in patients with advanced prostate cancer. It works by blocking enzymes needed for cancer growth, making it a valuable option for treating this type of cancer. ^{1 2 6 7 8}

Research Team

Ryan P Kopp, MD

Principal Investigator

VA Portland Health Care System, Portland, OR

Eligibility Criteria

Men over 18 with high-risk, non-metastatic prostate cancer that's not spread beyond the prostate and has specific genetic features (PTEN loss). They should have a life expectancy of more than 10 years, be able to take oral medication, and have no severe health issues. Men must use condoms if with a partner who can bear children. Those with active hepatitis or HIV, other cancers, significant heart disease or recent major surgery aren't eligible.

Inclusion Criteria

I am willing to give a tissue sample for testing.

I am scheduled for prostate surgery with lymph node removal.

I am a man who will use birth control when with a woman who can have children.

Exclusion Criteria

I have had treatments for prostate cancer, including hormone therapy, radiation, or chemotherapy.

Clinically significant abnormalities of glucose metabolism

I have not had major surgery or a serious injury recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Eligible patients undergo a 4-week run-in of intensified androgen deprivation therapy (iADT)

4 weeks

Treatment

Participants receive 16 weeks of combined iADT with AKT inhibition (capivasertib) prior to radical prostatectomy

16 weeks

Surgery

Participants undergo radical prostatectomy with assessment of pathological response

1 week

Follow-up

Participants are monitored for treatment-related adverse events and surgical complications

3 months

Treatment Details

Interventions

• Abiraterone Acetate
• Capivasertib

Trial Overview The trial is testing whether taking capivasertib along with intensified hormone therapy drugs (abiraterone acetate and leuprolide) before surgical removal of the prostate can shrink tumors in men whose cancer hasn't spread but is at high risk for progression.

Participant Groups

Group I: Single Arm Experimental Treatment 2 Interventions

neoadjuvant capivasertib combined with androgen receptor pathway therapy (leuprolide + abiraterone) prior to radical prostatectomy

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

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]

Abiraterone acetate is the first second-line hormonal treatment shown to improve survival in metastatic castration-resistant prostate cancer, initially approved in 2011 for patients who had not responded to docetaxel, showing a 4-month survival benefit.

The FDA has expanded its use to the pre-chemotherapy setting due to significant delays in disease progression and trends toward increased overall survival, with ongoing studies investigating its effectiveness in earlier stages and in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: targeting persistent androgen dependence in castration-resistant prostate cancer. Harshman, LC., Taplin, ME.[2021]

Abiraterone acetate has been shown to significantly increase survival rates in patients with metastatic castration-resistant prostate cancer, making it a key treatment option for this condition.

Recent studies indicate that abiraterone acetate is also effective when combined with androgen deprivation therapy for metastatic castration-sensitive prostate cancer, expanding its use in earlier stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate and its use in the treatment of metastatic prostate cancer: a review. Caffo, O., Veccia, A., Kinspergher, S., et al.[2018]

In a phase 3 trial with a median follow-up of 20.2 months, patients with metastatic castration-resistant prostate cancer who received abiraterone acetate and prednisone experienced significantly greater pain relief compared to those receiving prednisone alone, with 45% achieving pain palliation versus 28.8%.

Abiraterone acetate and prednisone also delayed the occurrence of skeletal-related events, with a median time of 25 months compared to 20.3 months for prednisone alone, indicating a substantial benefit in managing complications associated with bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Logothetis, CJ., Basch, E., Molina, A., et al.[2022]

In a study of 54 metastatic castration-resistant prostate cancer patients, cabazitaxel showed a PSA reduction rate of over 50% in 46.2% of patients, with a disease control rate of 83.3% after 3 months, although it had significant side effects like neutropenia in 40% of patients.

Abiraterone resulted in a PSA reduction rate of 35.1% and a disease control rate of 47.1%, with lower rates of severe hematotoxicities but higher rates of fatigue and other non-hematological side effects, indicating both treatments are effective with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Compassionate use of abiraterone and cabazitaxel: first experiences in docetaxel-pretreated castration-resistant prostate cancer patients]. Heck, MM., Höppner, M., Horn, T., et al.[2021]

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]

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]

Abiraterone acetate significantly improves overall survival and radiographic progression-free survival in men with metastatic castration-resistant prostate cancer (CRPC) when combined with prednisone, based on results from a multinational phase III study involving men who had previously received docetaxel.

The treatment is generally well-tolerated, although it can cause side effects like hypokalaemia and hypertension; however, serious adverse events were relatively low in the phase III studies, indicating it is a viable option for managing metastatic CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. Hoy, SM.[2021]

References

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

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

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

Abiraterone acetate: targeting persistent androgen dependence in castration-resistant prostate cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate and its use in the treatment of metastatic prostate cancer: a review. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. [2022]

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

[Compassionate use of abiraterone and cabazitaxel: first experiences in docetaxel-pretreated castration-resistant prostate cancer patients]. [2021]

6. 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]

7. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. [2021]