Study of TAS3681 in Metastatic Castration Resistant Prostate Cancer

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Taiho Pharma

Status and phase

Active, not recruiting
Phase 1

Conditions

Metastatic Castration Resistant Prostate Cancer

Treatments

Drug: TAS3681

Study type

Interventional

Funder types

Industry

Identifiers

NCT02566772
TO-TAS3681-101
2015-002745-55 (EudraCT Number)

Details and patient eligibility

About

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 (Escalation Phase) and to further evaluate safety and preliminary efficacy of TAS3681 at the MTD/recommended dose (Expansion Phase).

Full description

This is a first in human, multinational, Phase 1, open-label study of TAS3681 evaluating safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC) for which there is no standard therapy. Eligible participants will be enrolled to evaluate safety and determine the MTD/recommended dose for TAS3681, including a preliminary evaluation of food effect and antitumor activity. The study will be conducted in 2 parts, Dose Escalation (Enrollment closed) and Expansion (Enrollment Closed). Patients who are continuing to receive clinical benefit may receive drug in the extension part of the study after escalation and expansion are completed.

Enrollment

130 patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male ≥18 years of age

Histological or cytological evidence of metastatic castrate resistant prostate cancer (excluding neuroendocrine differentiation and small cell histology) who are castration resistant and have:

  • Dose escalation: documented progression defined in PCWG3 and/or intolerance to abiraterone and/or enzalutamide therapy, as well as 1 or more chemotherapies.

Expansion:

I. Group A: documented progression after abiraterone or enzalutamide and chemotherapy consisting of no more than 2 prior taxane-based therapies

ii. Group B: documented progression after only abiraterone or enzalutamide therapy without any chemotherapy

iii. Measurable disease per RECIST 1.1 and/or bone metastases

  • ECOG performance status of ≤1 on Day 1 Cycle 1
  • Ongoing androgen deprivation with serum testosterone <50 ng/dL
  • Expansion Phase only: willingness to undergo baseline core biopsies, if feasible
  • Ability to take medication orally
  • Adequate organ function
  • Agree to use effective contraception during the study and for 30 days after the last dose of TAS3681
  • Willing to comply with scheduled visits and procedures

Exclusion criteria

  • QTcF ≥ 450 ms, history of QTc prolongation or predisposition for QTc prolongation or family history of sudden cardiac death or QT prolongation
  • History or presence of heart failure or left ventricular dysfunction with ejection fraction <40% within the previous 6 months; if >6 months cardiac function within normal limits and free of cardiac-related symptoms
  • History or presence of atrial fibrillation, atrial flutter, or paroxysmal supraventricular tachycardia; the presence or history of ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia
  • Presence of cardiac pacemaker or implantable cardioverter-defibrillator
  • History or presence of bradycardia or conduction abnormalities
  • History or presence of cardiac arrest or unexplained syncope
  • Hypokalemia
  • History of myocardial infarction or severe unstable angina
  • Any medication administered within 2 weeks prior to 1st dose of TAS3681 that is known to prolong the QT interval or be arrhythmogenic
  • Received G-CSF, radiotherapy for extended field, anticancer chemotherapy, investigational agents, or major surgery within 4 weeks of study drug administration; receipt of anticoagulant or CYP3A inhibitor within 2 weeks of study drug administration
  • Serious illness or medical condition that could affect the safety or tolerability of study treatments
  • Received prior treatment with TAS3681
  • User of herbal products
  • Any condition or reason that in the opinion of the investigator, interferes with the ability of the participant to participate in the trial
  • To be eligible to participate in the food effect assessment (Escalation Phase only), participants must not have a history or presence of any clinically significant abnormality involving the gastrointestinal tract and an inability to fast for a minimum of 8 hours

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

130 participants in 1 patient group

TAS3681
Experimental group
Description:
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.
Treatment:
Drug: TAS3681

Trial contacts and locations

34

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Data sourced from clinicaltrials.gov

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