Capivasertib + Docetaxel for Prostate Cancer

(CAPItello280 Trial)

Recruiting at 204 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: AKT inhibitors, PI3K inhibitors

Disqualifiers: Diabetes, HIV, Hepatitis, 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 37 months

1035 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will assess the efficacy and safety of capivasertib plus docetaxel versus placebo plus docetaxel in participants with metastatic castration resistant prostate cancer (mCRPC), all participants will receive the docetaxel with steroid therapy and receive androgen deprivation therapy. The intention of the study is to demonstrate that the combination of capivasertib plus docetaxel is superior to placebo plus docetaxel with respect to the overall survival and/or the radiographic progression free survival of study participants.

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 strong inhibitors or inducers of CYP3A4, drugs that prolong the QT interval, or certain immunosuppressants close to the start of the trial. It's best to discuss your current medications with the trial team.

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

Research shows that Docetaxel, a component of the treatment, has been effective in treating advanced prostate cancer, reducing prostate-specific antigen levels and improving survival rates. It has shown promise both as a single agent and in combination with other drugs, suggesting potential benefits when combined with Capivasertib. ^{1 2 3 4 5}

What safety data exists for Capivasertib and Docetaxel in humans?

Docetaxel, a key drug in prostate cancer treatment, can cause side effects like low white blood cell count, hair loss, mouth sores, diarrhea, and nerve damage. Capivasertib has been studied in combination with docetaxel for prostate cancer, but specific safety data for this combination is not detailed in the provided research. ^{6 7 8 9 10}

How is the drug combination of Capivasertib and Docetaxel unique for treating prostate cancer?

The combination of Capivasertib and Docetaxel is unique because Capivasertib is a pan-AKT inhibitor that targets a specific pathway (PI3K/AKT/PTEN) often deregulated in advanced prostate cancer, and it has shown to improve overall survival in patients who have previously been treated with androgen receptor-targeted drugs. ^{6 11 12 13 14}

Eligibility Criteria

Men with advanced prostate cancer that's resistant to hormone therapy and has spread, despite previous treatments like abiraterone or enzalutamide. They should be fit for chemotherapy, have no severe heart issues or other serious illnesses, and must not have had certain recent surgeries or other cancer treatments.

Inclusion Criteria

I am mostly active and doctors expect me to live at least 12 more weeks.

My cancer has spread to my bones or soft tissues.

I have a suitable tissue sample from my tumor for testing.

Exclusion Criteria

I am not taking any medications that greatly affect my heart's rhythm.

I have not had major surgery in the last 4 weeks, except for minor procedures.

I don't have active brain tumors or spinal issues needing steroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive capivasertib or placebo in combination with docetaxel and steroids on a background of androgen deprivation therapy

up to approximately 37 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to approximately 46 months

Treatment Details

Interventions

• Capivasertib
• Docetaxel
• Placebo

Trial Overview The trial is testing if adding Capivasertib to standard Docetaxel chemotherapy improves survival in men with metastatic castration-resistant prostate cancer compared to placebo plus Docetaxel. All participants will continue hormone therapy alongside the study drugs.

Participant Groups

Group I: capivasertib + docetaxel Experimental Treatment 2 Interventions

Participants receive capivasertib in combination with docetaxel and steroids on a background of ADT.

Group II: placebo + docetaxel Placebo Group 2 Interventions

Participants receive placebo in combination with docetaxel and steroids on a background of ADT.

Capivasertib is already approved in United States, European Union for the following indications:

Approved in United States as Truqap for:

• Hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations

Approved in European Union as Truqap for:

• Locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alterations

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

In a phase II trial involving 84 patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), the combination of nivolumab and docetaxel showed a confirmed objective response rate (ORR) of 40% and a prostate-specific antigen response rate (PSA50-RR) of 46.9%.

The treatment demonstrated median radiographic progression-free survival (rPFS) of 9 months and overall survival (OS) of 18.2 months, with safety profiles consistent with the individual drugs, although there were three treatment-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus docetaxel in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer: results from the phase II CheckMate 9KD trial. Fizazi, K., González Mella, P., Castellano, D., et al.[2023]

Docetaxel shows a 42% response rate in treating androgen-independent prostate cancer based on four Phase II studies, indicating its significant efficacy as a single-agent therapy.

Combining docetaxel with estramustine may enhance response rates but also increases toxicity, and ongoing Phase III studies are expected to clarify the best use of docetaxel in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (taxotere) in the treatment of prostate cancer. Beer, TM., El-Geneidi, M., Eilers, KM.[2018]

Docetaxel-based treatments have shown effectiveness in managing advanced, androgen-independent prostate cancer, achieving significant palliative responses and reducing PSA levels by over 50% in patients.

Ongoing phase III trials are expected to provide crucial data on the impact of docetaxel on overall survival, while preliminary studies suggest that combining docetaxel with other novel agents is safe and may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in the integrated management of prostate cancer. Current applications and future promise. Logothetis, CJ.[2018]

The FDA has approved the combination of mitoxantrone and prednisone for hormone-refractory prostate cancer due to its superior palliative effects compared to steroids alone, based on two randomized trials.

A new phase III trial by the Southwest Oncology Group will compare the effectiveness of estramustine plus docetaxel against the standard treatment of mitoxantrone and prednisone, focusing on time to progression and survival, while also evaluating side effects and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) and estramustine versus mitoxantrone and prednisone for hormone-refractory prostate cancer: scientific basis and design of Southwest Oncology Group Study 9916. Hussain, M., Petrylak, D., Fisher, E., et al.[2018]

Docetaxel-based therapy has been shown to provide a survival benefit for men with metastatic prostate cancer, marking a significant advancement beyond palliative care options.

Ongoing trials are exploring various combination therapies with docetaxel, but the best timing for initiating treatment remains unclear due to a lack of prospective clinical trial data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current role of chemotherapy in metastatic hormone-refractory prostate cancer. Petrylak, DP.[2022]

In a phase II trial involving 150 patients with metastatic castration-resistant prostate cancer (mCRPC), the addition of capivasertib to standard chemotherapy did not significantly prolong composite progression-free survival (cPFS) compared to placebo, with median cPFS of 7.03 months for capivasertib versus 6.70 months for placebo.

However, capivasertib was associated with a significant improvement in overall survival (OS), with a median OS of 31.15 months for the capivasertib group compared to 20.27 months for the placebo group, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID). Crabb, SJ., Griffiths, G., Marwood, E., et al.[2022]

Cabazitaxel significantly improves overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) compared to mitoxantrone, with a median survival of 15.1 months versus 12.7 months, indicating its efficacy as a treatment option.

The safety profile of cabazitaxel is similar to that of first-generation taxanes, with manageable side effects such as diarrhea and neutropenia, which can be addressed through monitoring and supportive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cabazitaxel--a next-generation taxane for the treatment of patients with metastatic castration-resistant prostate cancer]. Ecstein-Fraisse, E., Su, Z.[2014]

References

1. England pubmed.ncbi.nlm.nih.gov

Nivolumab plus docetaxel in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer: results from the phase II CheckMate 9KD trial. [2023]

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

Docetaxel (taxotere) in the treatment of prostate cancer. [2018]

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

Docetaxel in the integrated management of prostate cancer. Current applications and future promise. [2018]

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

Docetaxel (Taxotere) and estramustine versus mitoxantrone and prednisone for hormone-refractory prostate cancer: scientific basis and design of Southwest Oncology Group Study 9916. [2018]

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

The current role of chemotherapy in metastatic hormone-refractory prostate cancer. [2022]

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

Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID). [2022]

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

Combination treatment with docetaxel and histone deacetylase inhibitors downregulates androgen receptor signaling in castration-resistant prostate cancer. [2019]

8. France pubmed.ncbi.nlm.nih.gov

[Chemotherapy in castrate-resistant metastatic prostate cancer]. [2013]

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

Docetaxel with or without estramustine for estramustine refractory castration-resistant prostate cancer: a single institution experience. [2021]

10. Japan pubmed.ncbi.nlm.nih.gov

Weekly, low-dose docetaxel combined with estramustine for Japanese castration-resistant prostate cancer: its efficacy and safety profile compared with tri-weekly standard-dose treatment. [2021]

11. Japan pubmed.ncbi.nlm.nih.gov

[Cabazitaxel--a next-generation taxane for the treatment of patients with metastatic castration-resistant prostate cancer]. [2014]

12. England pubmed.ncbi.nlm.nih.gov

Loss of SLCO1B3 drives taxane resistance in prostate cancer. [2021]

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

Phase II trial evaluating a docetaxel-capecitabine combination as treatment for hormone-refractory prostate cancer. [2018]

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

Overall Survival Update for Patients with Metastatic Castration-resistant Prostate Cancer Treated with Capivasertib and Docetaxel in the Phase 2 ProCAID Clinical Trial. [2022]