Hormone + Radiation Therapy with TAK-700 for Prostate Cancer

Recruiting at 171 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Radiation Therapy Oncology Group

Must be taking: Hormone therapy

Must not be taking: Glucocorticoids

Disqualifiers: Metastatic disease, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

239 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Androgens can cause the growth of prostate cancer cells. Drugs, such as steroid 17alpha-monooxygenase TAK-700, when used with other hormone therapy, may lessen the amount of androgens made by the body. Radiation therapy uses high energy x rays to kill tumor cells. This may be an effective treatment for prostate cancer when combined with hormone therapy. Studying quality-of-life in patients having cancer treatment may help identify the intermediate- and long-term effects of treatment on patients with prostate cancer. PURPOSE: This randomized phase III trial is studying the use of hormone therapy, including TAK-700, together with radiation therapy in treating patients with prostate cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on androgen deprivation therapy, you may continue it if you register within 50 days of starting it. Please consult with the trial team for specific guidance on your medications.

What data supports the effectiveness of the drug Bicalutamide (Casodex) in combination with radiation therapy for prostate cancer?

Research shows that adding Bicalutamide (Casodex) to standard care, including radiotherapy, significantly improves progression-free survival (the time during which the cancer does not get worse) in patients with early, non-metastatic prostate cancer. In one study, it reduced the risk of cancer progression by 34% compared to standard care alone. ^{1 2 3 4 5}

Is the combination of hormone therapy and radiation with TAK-700 safe for prostate cancer treatment?

Bicalutamide (Casodex), a component of the treatment, has been shown to be well-tolerated in clinical studies, with common side effects including breast tenderness, hot flushes, and gynecomastia (enlarged breast tissue in men). It is not associated with serious side effects like liver function changes or alcohol intolerance, and it has fewer gastrointestinal effects compared to other similar drugs. ^{1 3 6 7 8}

What makes the hormone and radiation therapy with TAK-700 unique for prostate cancer treatment?

This treatment combines hormone therapy with TAK-700, a novel drug that targets steroid 17alpha-monooxygenase, and radiation therapy, which may offer a more comprehensive approach by addressing both hormone-sensitive and radiation-responsive aspects of prostate cancer. The inclusion of TAK-700, which is not commonly used in standard treatments, could provide a new mechanism to inhibit cancer growth. ^{1 3 4 9 10}

Research Team

Dror Michaelson, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

Men aged 18+ with high-risk prostate cancer, who may have started hormone therapy within the last 50 days but haven't had certain treatments like chemotherapy for prostate cancer. They should not have other active cancers or serious heart, liver, or kidney diseases and must be willing to use contraception.

Inclusion Criteria

Agree to completely abstain from intercourse.

My recent scans show no cancer spread to distant parts of my body.

My bone scan was unclear, but X-rays showed no cancer spread.

Exclusion Criteria

Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel.

Q-wave infarction, unless identified 6 or more months prior to screening

I have a stomach or intestine condition that affects how I absorb pills.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Androgen Deprivation Therapy (ADT) Initiation

Standard androgen deprivation therapy (ADT) begins two months prior to radiation therapy (RT).

8 weeks

Radiation Therapy

Participants receive dose-escalated radiation therapy in combination with ADT.

8 weeks

TAK-700 Treatment

Participants receive TAK-700 in addition to standard ADT for 24 months.

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 3 months for 2 years, every 6 months for 1 year, and then annually.

5 years

Treatment Details

Interventions

• Bicalutamide
• Buserelin
• Flutamide
• Goserelin acetate
• Leuprolide acetate
• Radiation therapy
• Steroid 17alpha-monooxygenase TAK-700

Trial Overview This phase III trial is testing if adding TAK-700 to standard hormone therapy and radiation helps treat high-risk prostate cancer better. It also looks at how these treatments affect patients' quality of life over time.

Participant Groups

Group I: TAK-700 + ADT + RT Experimental Treatment 4 Interventions

TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.

Group II: ADT + RT Active Control 3 Interventions

Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.

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?

Radiation Therapy Oncology Group

Lead Sponsor

Trials

191

Recruited

64,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Findings from Research

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]

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, when used in conjunction with radiation therapy, showed cytotoxic effects in androgen-dependent prostate cancer cells (LNCaP), leading to cell cycle arrest and reduced expression of prostate serum antigen (PSA) and androgen receptor (AR).

The study found that bicalutamide decreased the effectiveness of radiation in LNCaP cells, suggesting that it should not be administered close to radiation treatment to avoid antagonistic interactions, while showing an additive effect in androgen-independent DU145 cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonistic interaction between bicalutamide (Casodex) and radiation in androgen-positive prostate cancer LNCaP cells. Quéro, L., Giocanti, N., Hennequin, C., et al.[2014]

A combination treatment of 150 mg bicalutamide and 5 mg finasteride was effective in achieving undetectable PSA levels and improving quality of life in a 69-year-old patient with relapsed prostate cancer, demonstrating minimal side effects.

Laboratory experiments showed that this combination therapy inhibited cancer cell proliferation and reduced androgen receptor activity, potentially slowing the progression to hormone independence in prostate cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The biological basis for the use of an anti-androgen and a 5-alpha-reductase inhibitor in the treatment of recurrent prostate cancer: Case report and review. Wang, LG., Mencher, SK., McCarron, JP., et al.[2014]

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]

References

1. 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]

2. 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]

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

Antagonistic interaction between bicalutamide (Casodex) and radiation in androgen-positive prostate cancer LNCaP cells. [2014]

4. 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]

5. Ireland pubmed.ncbi.nlm.nih.gov

Bicalutamide ('Casodex') 150 mg as adjuvant to radiotherapy in patients with localised or locally advanced prostate cancer: results from the randomised Early Prostate Cancer Programme. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Casodex (bicalutamide): overview of a new antiandrogen developed for the treatment of prostate cancer. [2019]

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

Tolerability and quality of life aspects with the anti-androgen Casodex (ICI 176,334) as monotherapy for prostate cancer. International Casodex Investigators. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical progress with a new antiandrogen, Casodex (bicalutamide). [2019]

9. Greece pubmed.ncbi.nlm.nih.gov

The biological basis for the use of an anti-androgen and a 5-alpha-reductase inhibitor in the treatment of recurrent prostate cancer: Case report and review. [2014]

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

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