Capivasertib + Docetaxel for Prostate Cancer

(CAPItello280 Trial)

Not currently recruiting at 256 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments to determine if they can improve survival and slow disease progression in men with metastatic castration-resistant prostate cancer (mCRPC). Participants will receive either capivasertib (a new potential drug) plus docetaxel or a placebo plus docetaxel, alongside standard hormone therapy. The goal is to determine if adding capivasertib can help patients live longer or delay cancer progression. This trial suits those with prostate cancer that has spread and continues to grow despite hormone therapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of capivasertib and docetaxel has been tested for safety in people with prostate cancer. Previous studies found that capivasertib's side effects were consistent with earlier findings, suggesting the treatment is generally well-tolerated, though some side effects may occur, as with many cancer treatments.

Docetaxel, a long-used chemotherapy drug, has a well-understood safety profile. While side effects can occur, they are often manageable. Participants should discuss potential side effects and any concerns with their doctor. Safety remains a key focus of these studies, and the treatment must be proven safe enough for testing in a large group of people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about capivasertib combined with docetaxel for prostate cancer because it offers a fresh approach to treatment. Unlike other prostate cancer therapies that primarily target hormone pathways, capivasertib works differently by inhibiting the AKT pathway, which is a key driver in cancer cell growth and survival. This dual-action strategy, combining capivasertib's novel mechanism with the proven efficacy of docetaxel, aims to enhance the overall effectiveness against prostate cancer. Additionally, this combination may provide an option for patients whose cancer has become resistant to existing hormone-based treatments.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

In this trial, participants will receive either capivasertib with docetaxel or a placebo with docetaxel. Research has shown that combining capivasertib with docetaxel may be promising for treating advanced prostate cancer that no longer responds to hormone therapy. Studies have found that capivasertib can help kill cancer cells more effectively when combined with docetaxel, potentially leading to longer survival. Early results suggest that capivasertib might also combat cancer cells resistant to other treatments. This combination aims to extend life and slow cancer growth, offering hope for better treatment outcomes. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 had cancer before, but it was treated over 2 years ago and is not likely to come back.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35688662/

Overall Survival Update for Patients with Metastatic ... Initial analysis of the ProCAID results suggested that capivasertib improved overall survival benefit. This follow-up analysis suggests that ...

2. nature.com nature.com/articles/s41416-024-02614-w

Capivasertib combines with docetaxel to enhance anti ... Taken together these data suggest that capivasertib treatment increases the level and rate of apoptosis of docetaxel-persister prostate cancer ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05348577

NCT05348577 | Study of Capivasertib + Docetaxel vs ... This study will assess the efficacy and safety of capivasertib plus docetaxel versus placebo plus docetaxel in participants with metastatic castration ...

4. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/Update-on-CAPItello-280-Phase-III-trial-of-TRUQAP-capivasertib-in-metastatic-castration-resistant-prostate-cancer.html

Update on CAPItello-280 Phase III trial of TRUQAP ... AstraZeneca is discontinuing the CAPItello-280 Phase III trial evaluating the efficacy and safety of TRUQAP (capivasertib) in combination with docetaxel and ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.TPS287

CAPItello-280: A phase III study of capivasertib and ... CAPItello-280 is a Phase III study to confirm the efficacy and safety of capivasertib in combination with docetaxel compared with placebo and docetaxel in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11014923/

Capivasertib combines with docetaxel to enhance anti- ... Taken together these data suggest that capivasertib treatment increases the level and rate of apoptosis of docetaxel-persister prostate cancer ...

7. onclive.com onclive.com/view/phase-3-study-of-capivasertib-plus-chemo-adt-in-mcrpc-to-end-after-recommendation-from-data-monitoring-committee

Phase 3 Study of Capivasertib Plus Chemo/ADT in ... Safety data for capivasertib were consistent with findings from previous clinical trials. CAPItello-280 was a randomized, double-blind, placebo- ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.108

Updated overall survival (OS) analysis for ProCAID Results: At this OS update, 99 pts (66.0%) had died, with 88 of these deaths (88.9%) due to prostate cancer. 5 pts (3.3%) remained on ...