Bicalutamide + MK2206 for Prostate Cancer

Recruiting at 228 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Antihormone therapy

Must not be taking: Antiepileptics, Antidepressants, Steroids, others

Disqualifiers: HIV, Cardiac conditions, GI disease, 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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 31 weeks

108 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well giving bicalutamide with or without Akt inhibitor MK2206 works in treating patients with previously treated prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of androgens made by the body. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether bicalutamide is more effective with or without Akt inhibitor MK2206 in treating prostate cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but certain medications are not allowed. You cannot take medications that affect testosterone levels, certain anti-epileptic drugs, or specific substances like St John's Wort and grapefruit. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Bicalutamide for prostate cancer?

Research shows that Bicalutamide, when used in combination with standard care, significantly reduces the risk of prostate cancer progression and improves progression-free survival in patients with early, non-metastatic prostate cancer. ^{1 2 3 4 5}

Is Bicalutamide safe for humans?

Bicalutamide (also known as Casodex) has been studied in various clinical trials for prostate cancer and is generally considered safe for use in humans. It has been approved in many countries and is used in combination with other treatments, showing good tolerability (ability to be taken without causing severe side effects) in patients. ^{2 3 5 6 7}

What makes the drug Bicalutamide + MK2206 unique for prostate cancer treatment?

Bicalutamide is a non-steroidal anti-androgen that blocks male hormones from stimulating prostate cancer growth, and it is often used in combination with other treatments. The combination with MK2206, which is an AKT inhibitor, is unique because it targets a different pathway involved in cancer cell survival, potentially offering a more comprehensive approach to treating prostate cancer. ^{1 2 3 5 6}

Research Team

Anna C Ferrari

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

Men with hormone-sensitive prostate cancer, who have had previous treatments like surgery or radiation, can join this trial. They should not have metastatic disease and must show a rise in PSA levels after primary therapy. Testosterone modulating therapies are not allowed within the last year unless used as neoadjuvant/adjuvant treatment.

Inclusion Criteria

Granulocytes >= 1,500/mm^3

Platelet count >= 100,000/mm^3

My PSA levels are between 2 and 50 ng/mL and stable or increasing.

Exclusion Criteria

Human immunodeficiency virus (HIV)-positive patients are excluded from this study

Right bundle branch block and left anterior hemi-block (bifascicular block)

I have severe heart failure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observation

Patients undergo observation to monitor PSA levels before starting treatment

12 weeks

Regular monitoring visits

Treatment

Patients receive bicalutamide and/or Akt inhibitor MK2206 based on randomization

31 weeks

Weekly visits for drug administration and monitoring

Extended Treatment

Patients with a PSA decline of >= 50% may continue treatment until week 72

28 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 3 months for 2 years, every 6 months for 3 years, then annually

Treatment Details

Interventions

• Akt Inhibitor MK2206
• Bicalutamide

Trial Overview The trial is testing if bicalutamide, an antihormone therapy that reduces androgens, works better alone or combined with Akt inhibitor MK2206 which blocks enzymes needed for tumor growth. It's for men whose prostate cancer has returned after initial treatment.

Participant Groups

Group I: Arm B (Akt inhibitor MK2206 and bicalutamide) Experimental Treatment 3 Interventions

Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (observation and bicalutamide) Active Control 3 Interventions

Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in United States as Casodex for:

• Metastatic prostate cancer

Approved in Japan as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in Canada as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Bicalutamide is a newly approved non-steroidal anti-androgen for prostate cancer treatment, showing strong affinity for androgen receptors and effective tumor suppression in pharmacological studies, leading to its approval in about 70 countries.

In a late Phase II study in Japan, bicalutamide achieved a response rate of 64.4% when used alone, highlighting its potential as a standalone treatment option that may enhance patient quality of life and sexual function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A new anti-androgen, bicalutamide (Casodex), for the treatment of prostate cancer--basic clinical aspects]. Akaza, H.[2014]

In a study involving 3603 men with localized or locally advanced prostate cancer, bicalutamide significantly reduced the risk of disease progression by 43% compared to placebo after a median follow-up of 2.6 years.

Bicalutamide also delayed the time to prostate-specific antigen (PSA) doubling, indicating its efficacy in managing prostate cancer, although common side effects included gynecomastia and breast pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bicalutamide (Casodex) 150 mg as immediate therapy in patients with localized or locally advanced prostate cancer significantly reduces the risk of disease progression. Wirth, M., Tyrrell, C., Wallace, M., et al.[2019]

In a 7-year study involving patients with early, non-metastatic prostate cancer, adding bicalutamide (150 mg) to standard care significantly improved progression-free survival (PFS) for those with locally advanced disease, reducing the risk of progression by 34%.

However, in cases of localized disease, bicalutamide did not show a significant benefit in PFS, and there was no difference in overall survival between the treatment and standard care groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bicalutamide (Casodex) 150 mg plus standard care in early non-metastatic prostate cancer: results from Early Prostate Cancer Trial 24 at a median 7 years' follow-up. Wirth, M., Tyrrell, C., Delaere, K., et al.[2014]

Bicalutamide, particularly at a 150-mg daily dose, is effective as a monotherapy for locally advanced prostate cancer, providing similar survival outcomes to castration, while also improving quality of life.

When combined with a luteinizing hormone-releasing hormone agonist (LHRH-A), a lower 50-mg daily dose of bicalutamide shows equivalent efficacy to flutamide, with the added benefit of better tolerability and longer median survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bicalutamide (Casodex) in the treatment of prostate cancer: history of clinical development. Kolvenbag, GJ., Blackledge, GR., Gotting-Smith, K.[2022]

In a study involving 1,218 patients with early prostate cancer, bicalutamide 150 mg significantly reduced the risk of disease progression by 57% compared to standard care alone, demonstrating its efficacy as an immediate therapy.

The study, with a median follow-up of 3 years, showed no difference in overall survival between bicalutamide and placebo, indicating that while it effectively delays disease progression, its impact on long-term survival is still being evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer. First report from the Scandinavian Prostatic Cancer Group Study No. 6. Iversen, P., Tammela, TL., Vaage, S., et al.[2019]

References

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

Bicalutamide ('Casodex') 150 mg in addition to standard care in patients with nonmetastatic prostate cancer: updated results from a randomised double-blind phase III study (median follow-up 5.1 y) in the early prostate cancer programme. [2014]

2. Japan pubmed.ncbi.nlm.nih.gov

[A new anti-androgen, bicalutamide (Casodex), for the treatment of prostate cancer--basic clinical aspects]. [2014]

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

Bicalutamide (Casodex) 150 mg as immediate therapy in patients with localized or locally advanced prostate cancer significantly reduces the risk of disease progression. [2019]

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

The bicalutamide 150 mg early prostate cancer program: findings of the North American trial at 7.7-year median followup. [2014]

5. England pubmed.ncbi.nlm.nih.gov

Bicalutamide (Casodex) 150 mg plus standard care in early non-metastatic prostate cancer: results from Early Prostate Cancer Trial 24 at a median 7 years' follow-up. [2014]

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

Bicalutamide (Casodex) in the treatment of prostate cancer: history of clinical development. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer. First report from the Scandinavian Prostatic Cancer Group Study No. 6. [2019]