TAS3681 for Prostate Cancer

Recruiting at 42 trial locations

Overseen By Elizabeth Calleja, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Taiho Oncology, Inc.

Must be taking: Androgen deprivation

Must not be taking: QT prolonging drugs, CYP3A inhibitors

Disqualifiers: Heart failure, Arrhythmias, Pacemaker, others

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

Compensation: Varies

Number of Visits: Unknown

130 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests TAS3681, a new drug, for safety and effectiveness in patients with advanced prostate cancer that doesn't respond to usual treatments. It aims to find out how the drug works in the body and its impact on cancer cells.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but you cannot take medications that prolong the QT interval or are arrhythmogenic (cause irregular heartbeats) within 2 weeks before starting the trial. Also, you should not take anticoagulants or CYP3A inhibitors within 2 weeks of starting the study drug.

What data supports the effectiveness of the drug TAS3681 for prostate cancer?

The research highlights that targeting androgen receptor signaling, which TAS3681 likely involves, is effective in controlling prostate cancer, especially in advanced stages. Similar drugs like abiraterone acetate have shown survival benefits in patients with advanced prostate cancer, suggesting that TAS3681 might also be effective. ^{1 2 3 4 5}

How is the drug TAS3681 different from other prostate cancer treatments?

TAS3681, also known as tasquinimod, is unique because it targets the S100A9 protein, which plays a role in regulating immune cells that can suppress the body's immune response to cancer. This drug has shown anti-angiogenic (preventing the formation of new blood vessels that tumors need to grow) and immune-modulatory properties, making it different from other treatments that primarily focus on hormone pathways or chemotherapy. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread. They should be in good physical condition, able to take oral medication, have adequate organ function, and agree to use contraception. Participants must not have heart issues or be taking certain other medications.

Inclusion Criteria

My prostate cancer is resistant to standard treatments and has spread.

I am willing to have a biopsy before the trial starts, if it's possible.

I am on hormone therapy for cancer, and my testosterone is below 50 ng/dL.

Exclusion Criteria

Hypokalemia

I have a history of slow heartbeat or heart signal issues.

I have a history of irregular heartbeats or arrhythmias.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive TAS3681 in 28-day cycles to determine the maximum tolerated dose (MTD) and assess safety and tolerability

6 months

Monthly visits

Expansion

Participants receive TAS3681 at the MTD/recommended dose to further evaluate safety and preliminary efficacy

6 months

Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants who continue to receive clinical benefit may receive TAS3681 in the extension part of the study

Long-term

Treatment Details

Interventions

• TAS3681

Trial Overview The study tests TAS3681's safety and the highest dose patients can tolerate without severe side effects (Escalation Phase), followed by further evaluation of its safety and initial effectiveness at this dose (Expansion Phase).

Participant Groups

Group I: TAS3681 Experimental Treatment 1 Intervention

All participants will receive TAS3681 in 28-day cycles. The Escalation phase includes participants who have progressed after abiraterone, enzalutamide and chemotherapy. Eleven dose escalation cohorts are planned, one of which includes a preliminary assessment of food effect. The MTD/recommended dose for further development will be used for participants in the Expansion Phase. The Expansion Phase will enroll participants who have progressed after abiraterone or enzalutamide with chemotherapy consisting of no more than 2 prior taxane-based therapies (Group A) or without any chemotherapy (Group B). Participants receive TAS3681 until discontinuation criteria are met.

Who Is Running the Clinical Trial?

Taiho Oncology, Inc.

Lead Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Findings from Research

Abiraterone acetate has been shown to improve overall survival in patients with castration-resistant prostate cancer (CRPC) who have previously been treated with docetaxel, highlighting that CRPC remains hormone-driven even in advanced stages.

There is a need for better molecular characterization of prostate cancer to identify different disease subsets, which could lead to more effective and personalized treatment strategies, including the development of predictive biomarkers for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting continued androgen receptor signaling in prostate cancer. Massard, C., Fizazi, K.[2015]

MDV3100, an androgen receptor antagonist, has been shown to improve survival in men with metastatic castration-resistant prostate cancer who have previously undergone docetaxel chemotherapy, indicating its efficacy in this patient population.

While comprehensive safety and efficacy data are still pending, MDV3100 is considered a well-tolerated option that could complement existing treatments for advanced prostate cancer, alongside other novel therapies like abiraterone and cabazitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MDV3100 for the treatment of prostate cancer. Mukherji, D., Pezaro, CJ., De-Bono, JS.[2021]

Tasquinimod has shown effectiveness in inhibiting the formation of metastases in castration-resistant prostate cancer, as demonstrated in both orthotopic and intratibial xenograft models.

The treatment appears to work by inducing molecular changes, such as upregulating thrombospondin 1 and downregulating hypoxia-driven genes, which contribute to its anti-angiogenic and anti-metastatic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of metastasis in a castration resistant prostate cancer model by the quinoline-3-carboxamide tasquinimod (ABR-215050). Jennbacken, K., Welén, K., Olsson, A., et al.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

TRIM36, a novel androgen-responsive gene, enhances anti-androgen efficacy against prostate cancer by inhibiting MAPK/ERK signaling pathways. [2022]

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

Targeting continued androgen receptor signaling in prostate cancer. [2015]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Time to Castration Resistance on Survival in Metastatic Hormone Sensitive Prostate Cancer Patients in the Era of Combination Therapies. [2022]

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

GPS Assay Association With Long-Term Cancer Outcomes: Twenty-Year Risk of Distant Metastasis and Prostate Cancer-Specific Mortality. [2022]

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

A 17-Gene Panel Genomic Prostate Score Has Similar Predictive Accuracy for Adverse Pathology at Radical Prostatectomy in African American and European American Men. [2022]

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

Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer. [2022]

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

A Phase II, Randomized, Open-Label, Multi-arm Study of TAS-115 for Castration-Resistant Prostate Cancer Patients With Bone Metastases. [2022]

8. England pubmed.ncbi.nlm.nih.gov

MDV3100 for the treatment of prostate cancer. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Tasquinimod in the treatment of castrate-resistant prostate cancer - current status and future prospects. [2020]

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

Inhibition of metastasis in a castration resistant prostate cancer model by the quinoline-3-carboxamide tasquinimod (ABR-215050). [2017]