Bicalutamide + MK2206 for Prostate Cancer

Not currently recruiting at 233 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether bicalutamide is more effective with or without the additional drug MK2206 in treating prostate cancer that has returned after initial treatment. Bicalutamide reduces hormones that help cancer grow, while MK2206, an Akt inhibitor, may block enzymes that enable tumor cells to grow. The trial seeks participants with prostate cancer that hasn't spread and who have experienced a rise in PSA levels, indicating a possible return of the cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in prostate cancer treatment.

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.

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

Research shows that bicalutamide is usually well-tolerated by patients with prostate cancer. This therapy lowers certain hormones, which can help slow cancer growth. Most patients experience mild side effects like hot flashes and slight liver changes, but these are generally manageable.

Studies have found that the Akt inhibitor MK2206 can be effective but may cause some issues. Some patients experience side effects like rash, diarrhea, and tiredness. Research indicates that drugs targeting the PI3K/AKT pathway, such as MK2206, can work well but often have more side effects than some other treatments.

Both treatments are being tested together to determine if they are more effective when combined. Regular check-ups are important to monitor any side effects for those who decide to join the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they combine bicalutamide, a well-known androgen receptor inhibitor, with MK2206, an experimental Akt inhibitor. Unlike standard treatments that primarily target androgen receptors alone, MK2206 works by blocking the Akt pathway, which is involved in cell survival and growth, offering a new mechanism of action that could be more effective for certain patients. This combination approach aims to enhance treatment effectiveness by attacking the cancer from multiple angles, potentially leading to better outcomes and longer remission periods for patients.

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

Studies have shown that bicalutamide can lower levels of androgens, hormones that can promote prostate cancer growth. By reducing these hormones, bicalutamide slows the cancer. In this trial, participants in Arm A will receive bicalutamide after an observation period. Research suggests that another drug, MK2206, might also help by inhibiting cancer cell growth. Lab studies have shown that MK2206 reduces the growth of prostate cancer cells. Participants in Arm B will receive both MK2206 and bicalutamide. Some reports indicate that combining MK2206 with other cancer drugs can enhance their effectiveness. Therefore, using bicalutamide with MK2206 might be more effective than using bicalutamide alone. ^{1 2 4 6 7}

Who Is on the Research Team?

Anna C Ferrari

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6662159/

Targeted AKT Inhibition in Prostate Cancer Cells and ... In summary, this study has shown that targeted AKT inhibition in prostate cancer cells result in a reduction of cell growth. This growth-inhibitory effect is ...

2. nature.com nature.com/articles/s41416-018-0242-3

Metabolic biomarkers of response to the AKT inhibitor MK ... Our results show that treatment with the AKT inhibitor MK-2206 results in metabolic changes detectable with MRS. Importantly, a decrease in the ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014299924006411

The efficacy and safety of PI3K and AKT inhibitors for ... According to pairwise meta-analysis, PI3K/AKT inhibitors showed to be highly effective, especially for treating mutant cancers, but had poor safety profiles.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01480154

Study Details | NCT01480154 | Akt Inhibitor MK2206 and ... This phase I trial studies the side effects and the best dose of Akt inhibitor MK2206 together with hydroxychloroquine in treating patients ...

5. aacrjournals.org aacrjournals.org/mct/article/9/7/1956/93857/MK-2206-an-Allosteric-Akt-Inhibitor-Enhances

MK-2206, an Allosteric Akt Inhibitor, Enhances Antitumor ... These results suggest that MK-2206 may significantly enhance the antitumor efficacy of docetaxel against breast tumors when administered in a stepwise schedule.

6. nature.com nature.com/articles/s41467-022-29655-0

Distinct resistance mechanisms arise to allosteric vs. ATP- ... Importantly, MK-2206 resistance can be overcome by treatment with ipatasertib, while ipatasertib resistance can be reversed by co-treatment with ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.3563

A phase II and co-clinical study of an AKT inhibitor in ... Based on strong preclinical mCRC and non-mCRC clinical data, we hypothesized that PI3K pathway inhibition may have clinical activity in mCRC pts ...