TAK-700 vs. Bicalutamide for Prostate Cancer

(S1216 Trial)

Not currently recruiting at 573 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Southwest Oncology Group

Must be taking: LHRH agonists

Must not be taking: Ketoconazole, Aminoglutethimide, Abiraterone, Enzalutamide

Disqualifiers: Brain metastases, Cardiac disease, Hypertension, HIV, 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: 3

Duration: 7 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks the best treatment for newly diagnosed metastatic prostate cancer, where the cancer has spread beyond the prostate. Researchers aim to determine whether combining TAK-700 (an experimental drug) with standard hormone therapy (androgen deprivation therapy or ADT) extends patient survival more effectively than ADT combined with bicalutamide. Individuals diagnosed with metastatic prostate cancer, who have normal testosterone levels and a PSA level of 2 or higher, might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, providing an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be willing to switch to bicalutamide or TAK-700 if you are currently on an antiandrogen. Concurrent use of certain medications like ketoconazole and experimental therapies is not allowed.

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, is generally safe for patients with prostate cancer. Studies have found that patients taking TAK-700 often experience a drop in PSA levels, which helps track the progress of prostate cancer. This decrease is a positive sign of the treatment's effectiveness and suggests the drug is relatively safe.

In earlier studies, patients taking 300 mg or more of TAK-700 had promising results with manageable side effects. While some side effects may occur, they usually aren't severe enough to stop treatment, allowing most patients to continue without major problems.

Bicalutamide, another treatment for prostate cancer, has been widely used and is known to be well-tolerated, with mostly mild to moderate side effects.

Overall, both TAK-700 and bicalutamide have demonstrated general safety for patients, with common side effects not posing major risks. However, as with any treatment, individual reactions may vary, so discussing potential risks with a healthcare provider is advisable. ^{1 2 3 4 5}

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

Researchers are excited about TAK-700 for prostate cancer because, unlike standard treatments like Bicalutamide, TAK-700 works by inhibiting a specific enzyme called CYP17A1. This enzyme is crucial for the production of androgens, which fuel the growth of prostate cancer cells. By directly targeting and reducing androgen levels, TAK-700 offers a potentially more effective way to manage prostate cancer progression compared to traditional androgen deprivation therapies.

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

This trial will compare the effectiveness of TAK-700 and Bicalutamide for prostate cancer. Research has shown that TAK-700, also known as orteronel, may help treat prostate cancer. In earlier studies, patients taking TAK-700 lived for an average of 17 months, compared to 15.2 months for those taking a placebo. Although this suggests some benefit, it did not achieve the main goal of significantly increasing survival time. TAK-700 has proven effective and generally well-tolerated in patients whose prostate cancer does not respond to standard treatments. Meanwhile, Bicalutamide is a well-known treatment often used with other therapies for prostate cancer. It works by blocking male hormones that can help cancer grow. Participants in this trial will receive either TAK-700 or Bicalutamide in combination with androgen deprivation therapy (ADT). ^{1 2 4 6 7}

Who Is on the Research Team?

Neeraj Agarwal, M.D.

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

This trial is for men with newly diagnosed metastatic prostate cancer who have a good performance status, meaning they can carry out daily activities with little to no assistance. They must have adequate liver, heart, and kidney function, agree to use contraception if of reproductive potential, and not have any serious illnesses that could interfere with the study. Men previously treated for other cancers may be eligible if they are in remission.

Inclusion Criteria

Adequate hematologic function as evidenced by leukocytes ≥ 3,000/mcL, absolute neutrophil count (ANC) ≥ 1,500/mcL, hemoglobin ≥ 9 g/dL, and platelets ≥ 100,000/mcL

DEXA scan within 2 years prior to registration

ECG within 42 days prior to registration and QTc interval ≤ 460 msec

Exclusion Criteria

Concurrent use of experimental therapy is not allowed

Hypersensitivity to TAK-700, to TAK-700 metabolites, to bicalutamide, or to LHRH agonists

It has been over 30 days since my last hormone therapy for prostate cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive androgen deprivation therapy (ADT) with either TAK-700 or Bicalutamide

7 months

Visits every 3 months for LHRH agonist administration

Follow-up

Participants are monitored for safety, effectiveness, and overall survival

9 years

Long-term Follow-up

Participants are monitored for long-term survival outcomes

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Bicalutamide
• TAK-700

Trial Overview The study aims to compare the effectiveness of two treatments on overall survival rates: one group will receive TAK-700 plus standard hormone therapy (ADT), while another group will get bicalutamide along with ADT. Participants are randomly assigned to either treatment path.

How Is the Trial Designed?

Group I: ADT + TAK-700 Experimental Treatment 1 Intervention

LHRH agonist - given as approved for androgen deprivation at a dose necessary to maintain castrate levels and equivalent to 22.5 mg of Leuprolide IM every 3 months. TAK-700, 300 mg, PO, twice daily

Group II: ADT + Bicalutamide Active Control 1 Intervention

LHRH agonist - given as approved for androgen deprivation at a dose necessary to maintain castrate levels and equivalent to 22.5 mg of Leuprolide IM every 3 months. Bicalutamide, 50 mg, PO, q daily

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?

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Millennium Pharmaceuticals, Inc.

Industry Sponsor

Trials

406

Recruited

46,900+

Dr. Christophe Bianchi

Millennium Pharmaceuticals, Inc.

Chief Medical Officer since 2006

MD from University of Geneva

Dr. Deborah Dunsire

Millennium Pharmaceuticals, Inc.

Chief Executive Officer since 2005

MD from University of Witwatersrand

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 124 patients with advanced prostate cancer, bicalutamide showed an overall response rate of 50% to 61% across different doses, with the 80 mg dose demonstrating the highest efficacy in reducing prostate lesions and metastases.

Bicalutamide was found to be well tolerated, with a similar incidence of adverse reactions (around 61-65%) across all doses, and the most common side effects being gynecomastia and breast pain, leading to the conclusion that 80 mg once daily is the recommended dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer]. Kotake, T., Usami, M., Isaka, S., et al.[2015]

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 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]

Citations

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

Orteronel for the treatment of prostate cancer - PMC The median overall survival was 17.0 months (95% CI: 15.2–19.9) in the orteronel arm versus 15.2 months (95% CI: 13.5–16.9) in the placebo arm (HR: 0.886 [95% ...

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

Updated data from a phase I/II study. Conclusions: TAK-700 ≥300 mg BID appears active and well tolerated in pts with mCRPC, with similar efficacy ± prednisone. Preclinical data and changes in ...

3. ascopubs.org ascopubs.org/doi/10.1200/jco.2014.32.4_suppl.7

Results from a phase 3, randomized, double-blind ... The study was terminated for failing to meet its primary endpoint: median overall survival (OS) was 17.0 months (95% CI 15.2, 19.9) in patients ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01046916

Safety and Efficacy Study of TAK-700 in Patients With ... This is a multicenter phase 2 open-label single-arm study that will evaluate the safety and efficacy of TAK-700 in patients with castration-resistant prostate ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/20/16/4218/13273/Phase-II-Study-of-Single-Agent-Orteronel-TAK-700

Phase II Study of Single-Agent Orteronel (TAK-700) in Patients ... The primary endpoint was percentage of patients achieving PSA ≤0.2 ng/mL (undetectable levels) at 3 months. Secondary endpoints included safety, PSA response, ...

6. ascopubs.org ascopubs.org/doi/10.1200/jco.2010.28.15_suppl.3084

Safety, pharmacokinetics, and efficacy of TAK-700 in ... All patients treated with ≥300 mg had a PSA decrease; of 15 pts who received TAK-700 ≥300 mg for ≥3 cycles and had a 3-month PSA determination, ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24965748/

Phase II study of single-agent orteronel (TAK-700) in ... PSA decreased >30% in 35 patients and 6 (16%) achieved PSA ≤ 0.2 ng/mL at 3 months. Median times to PSA progression and metastasis were 13.8 and ...