TAK-700 vs. Bicalutamide for Prostate Cancer

(S1216 Trial)

Recruiting at 559 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

1313 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare overall survival in newly diagnosed metastatic prostate cancer patients randomly assigned to androgen deprivation therapy (ADT) + TAK-700 versus ADT + bicalutamide.

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.

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

Research shows that Bicalutamide, when used as immediate therapy or alongside other treatments, significantly reduces the risk of prostate cancer progression and delays the doubling of prostate-specific antigen (PSA) levels in patients with localized or locally advanced prostate cancer. ^{1 2 3 4 5}

Is bicalutamide generally safe for humans?

Bicalutamide, also known as Casodex, has been shown to be generally well-tolerated in clinical studies for prostate cancer, with common side effects including breast pain and gynecomastia (enlarged breast tissue in men). Most patients tolerated the treatment well, although some experienced adverse reactions. ^{1 3 5 6 7}

How does the drug TAK-700 differ from other prostate cancer treatments?

TAK-700 is unique because it is being compared directly to bicalutamide, a well-established drug for prostate cancer, to evaluate its effectiveness. While bicalutamide is used as immediate therapy for localized or locally advanced prostate cancer, TAK-700's novel aspect lies in its potential to offer an alternative with possibly different mechanisms or benefits. ^{1 2 3 5 8}

Research Team

Neeraj Agarwal, M.D.

Principal Investigator

University of Utah

Eligibility Criteria

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

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

I am currently using LHRH antagonists like Degarelix.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. 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]

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

Is the efficacy of hormonal therapy affected by lymph node status? data from the bicalutamide (Casodex) Early Prostate Cancer program. [2014]

3. 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]

4. 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]

5. 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]

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

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

7. Japan pubmed.ncbi.nlm.nih.gov

[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer]. [2015]

8. 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]