Capivasertib + Abiraterone for Prostate Cancer

(CAPItello-281 Trial)

Recruiting at 280 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Androgen deprivation therapy

Must not be taking: Strong CYP3A4 inducers

Disqualifiers: Diabetes, Heart disease, Lung disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 55 months

1012 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will assess the efficacy and safety of capivasertib plus abiraterone (+prednisone/prednisolone) plus androgen deprivation therapy (ADT) versus placebo plus abiraterone (+prednisone/prednisolone) plus ADT in participants with mHSPC whose tumours are characterised by PTEN deficiency. The intention of the study is to demonstrate that in participants with mHSPC, the combination of capivasertib plus abiraterone (+prednisone/prednisolone) plus ADT is superior to placebo plus abiraterone (+prednisone/prednisolone) plus ADT in participants with mHSPC characterised by PTEN deficiency with respect to radiographic progression-free survival (rPFS) per 1) Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for soft tissue and/or Prostate Cancer Working Group (PCWG3) for bone as assessed by the investigator 2) death due to any cause.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that certain drugs, like strong inhibitors or inducers of CYP3A4, should be stopped 2-3 weeks before starting the study treatment. It's best to discuss your current medications with the study team to see if any adjustments are needed.

What data supports the effectiveness of the drug Capivasertib + Abiraterone for prostate cancer?

Research shows that Abiraterone acetate, when used with prednisone, significantly improves survival and delays disease progression in patients with metastatic castration-resistant prostate cancer. It has been effective both in patients who have and have not received prior chemotherapy. ^{1 2 3 4 5}

Is the combination of Capivasertib and Abiraterone safe for humans?

Abiraterone acetate, used in prostate cancer treatment, is generally well-tolerated but can cause side effects like low potassium levels, high blood pressure, fluid retention, and liver issues. The safety of Capivasertib in combination with Abiraterone specifically isn't detailed here, but Abiraterone alone has an acceptable safety profile in clinical settings. ^{1 2 6 7 8}

What makes the drug Capivasertib + Abiraterone unique for prostate cancer treatment?

The combination of Capivasertib and Abiraterone is unique because it targets both androgen production and signaling pathways involved in prostate cancer progression, potentially offering a more comprehensive approach than Abiraterone alone, which primarily inhibits androgen synthesis. ^{1 2 6 7 8}

Eligibility Criteria

Men with metastatic hormone-sensitive prostate cancer and PTEN deficiency, who can take abiraterone and steroids, are eligible. They must have a recent diagnosis (within 180 days), provide specific tissue samples, show evidence of metastasis, be on ADT treatment for up to 93 days before the trial starts, have an ECOG performance status of 0-1, and agree to contraception. Exclusions include brain metastases or spinal cord compression not stable without steroids for at least four weeks.

Inclusion Criteria

I can provide a tissue sample that is not from bone metastases.

I have completed the required pain and fatigue questionnaires.

I can take and keep down pills.

Exclusion Criteria

I cannot properly absorb medications due to my stomach or bowel condition.

I have not had major surgery in the last 4 weeks.

Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive capivasertib plus abiraterone (prednisone/prednisolone) plus ADT or placebo plus abiraterone (prednisone/prednisolone) plus ADT

Up to approximately 55 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including radiographic progression-free survival and overall survival

Up to approximately 80 months

Treatment Details

Interventions

• Abiraterone Acetate
• Capivasertib
• Placebo

Trial Overview The study is testing if adding Capivasertib to Abiraterone (+prednisone/prednisolone) along with ADT provides better outcomes than placebo plus Abiraterone (+prednisone/prednisolone) with ADT in men whose tumors lack PTEN protein. The main goal is improving time without disease progression using imaging criteria or until death from any cause.

Participant Groups

Group I: Capivasertib + Abiraterone Experimental Treatment 2 Interventions

Participants receive capivasertib in combination with abiraterone (prednisone/prednisolone) on a background of ADT.

Group II: Placebo + Abiraterone Placebo Group 2 Interventions

Participants receive placebo in combination with abiraterone (prednisone/prednisolone) on a background of ADT.

Abiraterone Acetate is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Zytiga for:

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

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Newly diagnosed high-risk metastatic hormone-sensitive prostate cancer

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

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]