TAS3681 for Prostate Cancer

No longer recruiting at 44 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TAS3681, an experimental drug for prostate cancer that resists standard hormone therapy and has metastasized. The main goal is to assess the safety and tolerability of this treatment and to identify the best dose for future use. The trial involves two phases: one to determine the ideal dose and another to further evaluate safety and early effectiveness. Men whose prostate cancer has not improved after treatments like abiraterone, enzalutamide, or possibly chemotherapy might be suitable candidates. Participants will take the treatment in 28-day cycles until they meet the criteria for stopping. As a Phase 1 trial, this research focuses on understanding how TAS3681 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that TAS3681 is likely to be safe for humans?

Research has shown that TAS3681, a treatment under study for prostate cancer, is generally safe. In earlier studies, patients who had tried many other treatments and were resistant to them tolerated TAS3681 well. The treatment also demonstrated its potential to fight cancer cells.

Another study tested different doses of TAS3681, ranging from 25 to 600 mg, and found it was well-tolerated at these levels. However, increasing the dose to 800 mg did not enhance drug benefits, suggesting higher doses might not be necessary.

Overall, TAS3681 appears safe, with patients handling the treatment without major problems. ^{1 2 3 4 5}

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

Unlike the standard treatments for prostate cancer, which often involve hormone therapies like abiraterone and enzalutamide, TAS3681 offers a unique approach by targeting androgen receptor pathways differently. Researchers are excited about TAS3681 because it could provide an option for patients who have already progressed after current hormone therapies and chemotherapy. This treatment is designed to continue working even when the cancer becomes resistant to other hormone therapies, potentially offering a new lifeline for patients with advanced prostate cancer.

What evidence suggests that TAS3681 might be an effective treatment for prostate cancer?

Research has shown that TAS3681 blocks certain proteins that promote prostate cancer growth. In studies, TAS3681 proved effective for patients with advanced prostate cancer who had previously tried treatments like abiraterone and enzalutamide, but their cancer continued to progress. Participants in this trial will receive TAS3681, which aims to interrupt the signals causing resistance to these drugs. Early findings suggest that TAS3681 is safe and may be effective even for patients whose cancer resists other treatments. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11306513/

TAS3681, an androgen receptor antagonist, prevents drug ... Our results demonstrate that TAS3681 suppresses the reactivation of AR signaling, which causes resistance to ARSIs, via a newly identified mechanism of action.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.5031

First-in-human study of TAS3681, an oral androgen ... TAS3681 has a manageable safety profile and has antitumor activity against heavily pretreated, multi-drug resistant mCRPC. The study expansion ...

3. urotoday.com urotoday.com/conference-highlights/asco-2021/asco-2021-prostate-cancer/129931-asco-2021-first-in-human-study-of-tas3681-an-oral-androgen-receptor-antagonist-with-ar-and-ar-splice-variant-downregulation-activity-in-patients-with-mcrpc-refractory-to-abiraterone-and-or-enzalutamide-and-chemotherapy.html

ASCO 2021: First-in-Human Study of TAS3681, an Oral ... The primary endpoints for this trial included the incidence of dose-limiting toxicities and adverse events. Other endpoints included pharmacokinetics and ...

4. withpower.com withpower.com/trial/phase-1-prostatic-neoplasms-2-2016-139dd

TAS3681 for Prostate Cancer · Info for Participants Abiraterone acetate has been shown to improve overall survival in patients with castration-resistant prostate cancer (CRPC) who have previously been treated ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.6_suppl.197

The impact of TAS3681, a new type of androgen receptor ... Results: In prostate cancer (PCa) cells which overexpress AR, in contrast to enzalutamide, TAS3681 effectively suppressed AR transactivation and cell ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02566772

NCT02566772 | Study of TAS3681 in Metastatic Castration ... The purpose of this trial is to investigate the safety and tolerability of TAS3681, to find the maximum tolerated dose (MTD)/recommended dose of TAS3681 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4896735/

Novel mechanism-based therapeutics for androgen axis ... TAS3681 is another agent in development that potentially possessed both anti-androgen and AR downregulation properties. TAS3681 exhibits in vitro and in vivo ...

8. bioworld.com bioworld.com/articles/684130-tas-3681-shows-safety-and-antitumor-activity-against-heavily-pretreated-multidrug-resistant-mcrpc

TAS-3681 shows safety and antitumor activity against ... PK data on q.d. administration showed TAS-3681 exposure increased dose-dependently with doses 25 to 600 mg, with no clear increase for 800 to ...