Hormone + Radiation Therapy with TAK-700 for Prostate Cancer

No longer recruiting at 180 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining a new drug, TAK-700 (a steroid 17alpha-monooxygenase inhibitor), with hormone therapy and radiation can effectively treat prostate cancer. Researchers believe TAK-700 may reduce the hormones that promote prostate cancer cell growth. The study will also examine the long-term effects of these treatments on patients' quality of life. Men with prostate cancer who have a high risk of recurrence and no sign of disease spreading might be eligible to join. 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.

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.

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

Research has shown that TAK-700, also known as Orteronel, was well tolerated in past studies. Patients with prostate cancer taking TAK-700 experienced a reduction in cancer-related markers, and the treatment was generally well tolerated. Common side effects include tiredness and stomach issues, but these can be managed.

Standard hormone treatments like Bicalutamide, Buserelin, Flutamide, Goserelin acetate, and Leuprolide acetate are widely used and generally considered safe. They may cause side effects such as hot flashes, fatigue, and mood changes.

Overall, previous studies have demonstrated that the treatments in this trial are safe, with side effects that are usually manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TAK-700 for prostate cancer because it targets the condition differently than most standard treatments. While typical therapies like androgen deprivation therapy (ADT) focus on reducing male hormones that fuel cancer growth, TAK-700 inhibits a specific enzyme called steroid 17alpha-monooxygenase, which plays a crucial role in testosterone production. This unique mechanism may enhance the effectiveness of existing hormone therapies and offers the potential for better long-term control of prostate cancer. Additionally, TAK-700 is used in combination with ADT and radiation therapy, which could provide a more comprehensive approach to managing the disease.

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

This trial will compare two treatment approaches for prostate cancer. One group of participants will receive standard androgen deprivation therapy (ADT) combined with radiation therapy (RT). Another group will receive TAK-700 in addition to ADT and RT. Research has shown that TAK-700, when used with hormone therapy, can significantly lower levels of PSA (a marker for prostate cancer), DHEA-S, and testosterone, which are linked to the growth of prostate cancer cells. Previous patients demonstrated positive responses to this treatment, indicating its potential effectiveness. TAK-700 blocks the production of certain hormones that can help prostate cancer grow. When combined with radiation therapy, it aims to kill cancer cells more effectively. Overall, using TAK-700 with hormone and radiation therapy may offer a promising way to treat prostate cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

Dror Michaelson, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01546987

Study Details | NCT01546987 | Hormone Therapy, ... 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25556680/

Phase 1/2 study of orteronel (TAK-700), an investigational 17 ... Conclusions: Orteronel plus DP was tolerable, with substantial reductions in PSA, DHEA-S, and testosterone levels, and evidence for measurable disease responses ...

3. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT01546987

UCSF Prostate Cancer Trial → Hormone Therapy, Radiation ... Drugs, such as steroid 17alpha-monooxygenase TAK-700, when used with other hormone therapy, may lessen the amount of androgens made by the body.

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT01546987/hormone-therapy-radiation-therapy-and-steroid-17alpha-monooxygenase-tak-700-in-treating-patients-with-high-risk-prostate-cancer

Hormone Therapy, Radiation Therapy, and Steroid ... Drugs, such as steroid 17alpha-monooxygenase TAK-700, when used with other hormone therapy, may lessen the amount of androgens made by the body.

5. asco.org asco.org/abstracts-presentations/ABSTRACT81633

Updated data from a phase I/II study. Mean circulating tumor cell numbers also decreased in all groups. Conclusions: TAK-700 ≥300 mg BID appears active and well tolerated in pts with mCRPC, with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4148348/

Orteronel for the treatment of prostate cancer - PMC Orteronel (also known as TAK-700) is a novel hormonal therapy that is currently in testing for the treatment of prostate cancer.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10705205/

Review of Current Treatment Intensification Strategies for ... This review summarizes the latest available outcome results of pivotal trials and clinical studies on the efficacy of TI. Keywords: radiotherapy/radiation ...