Capivasertib + Abiraterone for Prostate Cancer
(SNARE Trial)
Recruiting in Palo Alto (17 mi)
+3 other locations
Overseen byRyan P Kopp, MD
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Prior Safety Data
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.
12345What 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.
12678Is 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.
12678Eligibility 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.
+11 more
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.
+13 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Single ArmExperimental Treatment2 Interventions
neoadjuvant capivasertib combined with androgen receptor pathway therapy (leuprolide + abiraterone) prior to radical prostatectomy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
James J. Peters VA Medical Center, Bronx, NYBronx, NY
VA Greater Los Angeles Healthcare System, West Los Angeles, CAWest Los Angeles, CA
VA Puget Sound Health Care System Seattle Division, Seattle, WASeattle, WA
VA Portland Health Care System, Portland, ORPortland, OR
Who Is Running the Clinical Trial?
VA Office of Research and DevelopmentLead Sponsor
References
Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]Oral abiraterone acetate (Zytiga®), a selective cytochrome P450 17A1 enzyme inhibitor, is used in combination with prednisone or prednisolone to treat patients with metastatic castration-resistant prostate cancer (CRPC) who have previously received docetaxel-containing chemotherapy. In a clinical trial in patients with CRPC, abiraterone acetate plus prednisone significantly prolonged overall survival, the time to prostate-specific antigen progression and progression-free survival compared with placebo plus prednisone.
Abiraterone acetate: targeting persistent androgen dependence in castration-resistant prostate cancer. [2021]Abiraterone acetate is the first second-line hormonal agent proven to improve survival in metastatic castration-resistant prostate cancer. It selectively inhibits cytochrome P450 17 (CYP17) α-hydroxylase and cytochrome17,20 (C17,20)-lyase, which are enzymes critical for androgen synthesis. Abiraterone acetate was initially approved in the United States in 2011 after demonstrating a 4-month survival benefit in docetaxel-refractory metastatic prostate cancer. The FDA recently expanded its indication for use in the pre-chemotherapy setting after it elicited significant delays in disease progression and a strong trend for increased overall survival in phase III studies. Ongoing investigations of abiraterone are evaluating its efficacy in earlier disease states, exploring its synergy in combination with other therapeutic agents, and assessing the necessity for administration of concurrent steroids and gonadal suppression. The identification and development of predictive biomarkers will optimize the incorporation of abiraterone into the management of advanced prostate cancer.
Abiraterone acetate and its use in the treatment of metastatic prostate cancer: a review. [2018]Abiraterone acetate, which targets enzymatic complexes playing a central role in steroidogenesis, demonstrated to increase survival significantly in both chemo-naive and docetaxel pretreated, becoming one of the drugs of choice for metastatic castration-resistant prostate cancer. More recently, this agent in combination to androgen deprivation therapy demonstrated to be efficacious also in metastatic castration-sensitive prostate cancer. The present review is aimed to outline the clinical development of abiraterone acetate, the pivotal trials which led to its approval for the clinical practice, new evidence about its efficacy in metastatic castration-sensitive prostate cancer, its place in the therapeutic landscape of prostate cancer and future directions of development.
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]Bone metastases are a major cause of morbidity in metastatic castration-resistant prostate cancer. Abiraterone acetate potently disrupts intracrine androgen receptor signalling pathways implicated in the progression of the disease, including bone metastases. We assessed data for pain control and skeletal-related events prospectively collected as part of the randomised, phase 3 COU-AA-301 trial of abiraterone acetate plus prednisone versus placebo plus prednisone in patients with metastatic castration-resistant prostate cancer after docetaxel chemotherapy.
[Compassionate use of abiraterone and cabazitaxel: first experiences in docetaxel-pretreated castration-resistant prostate cancer patients]. [2021]First clinical experiences with abiraterone and cabazitaxel for the treatment of metastatic castration-resistant prostate cancer patients following docetaxel chemotherapy are reported.
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]Abiraterone acetate is a highly variable drug and has been approved for the treatment of patients with metastatic castration-resistant prostate cancer in many countries. This study was conducted to compare the pharmacokinetic profile between the test product (abiraterone acetate tablet) and reference product ZYTIGA® (250 mg) mainly.
Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. [2020]Abiraterone acetate, marketed as Zytiga®, is an antiandrogen medication used in the treatment of prostate cancer. Abiraterone acetate is a BCS Class IV compound associated with several oral delivery challenges. Its low solubility and high lipophilicity lead to poor oral bioavailability (
Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. [2021]Abiraterone acetate (Zytiga(®)) is an orally administered, selective inhibitor of the 17α-hydroxylase and C17,20-lyase enzymatic activities of cytochrome P450 (CYP) 17. CYP17 is required for androgen biosynthesis, with androgen receptor signalling crucial in the progression from primary to metastatic prostate cancer. Abiraterone acetate is approved in the European Union and the US, in combination with prednisone or prednisolone, for the treatment of men with metastatic castration-resistant prostate cancer (CRPC). When administered in combination with prednisone in a placebo-controlled, multinational phase III study, abiraterone acetate significantly prolonged overall survival and radiographic progression-free survival (rPFS) in men with metastatic CRPC who had previously received docetaxel. In men with metastatic CRPC who had not previously received chemotherapy participating in a placebo-controlled, multinational phase III study, there was a strong trend towards an overall survival benefit, a significant prolongation in rPFS and significant delays in clinical decline, the need for chemotherapy and the onset of pain observed. Given the nature of the therapy, the overall tolerability profile of abiraterone acetate, in combination with prednisone, was acceptable in men with metastatic CRPC. Abiraterone acetate is associated with hypokalaemia, hypertension, and fluid retention or oedema, secondary to its mechanism of action, and with cardiac adverse events and hepatotoxicity; however, in the phase III studies the incidences of the most frequently reported grade 3 or 4 adverse events of special interest were relatively low. Although the final overall survival data in men with metastatic CRPC who have not previously received chemotherapy are awaited, current evidence indicates that abiraterone acetate is a useful option for the treatment of metastatic CRPC.