Study of TAS3681 in Metastatic Castration Resistant Prostate Cancer

NCT ID: NCT02566772

Last Updated: 2024-09-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2024-04-26

Brief Summary

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).

Detailed 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.

Conditions

Metastatic Castration Resistant Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TAS3681

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.

Group Type: EXPERIMENTAL

TAS3681

Intervention Type: DRUG

TAS3681 will be provided as 100 mg tablets to be administered orally in 28-day cycles. The number of cycles is approximately 6, or until discontinuation criteria is met.

Interventions

TAS3681

TAS3681 will be provided as 100 mg tablets to be administered orally in 28-day cycles. The number of cycles is approximately 6, or until discontinuation criteria is met.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male ≥18 years of age

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

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

2. 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

3. ECOG performance status of ≤1 on Day 1 Cycle 1

4. Ongoing androgen deprivation with serum testosterone <50 ng/dL

5. Expansion Phase only: willingness to undergo baseline core biopsies, if feasible

6. Ability to take medication orally

7. Adequate organ function

8. Agree to use effective contraception during the study and for 30 days after the last dose of TAS3681

9. Willing to comply with scheduled visits and procedures

Exclusion Criteria

1. QTcF ≥ 450 ms, history of QTc prolongation or predisposition for QTc prolongation or family history of sudden cardiac death or QT prolongation

2. 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

3. 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

4. Presence of cardiac pacemaker or implantable cardioverter-defibrillator

5. History or presence of bradycardia or conduction abnormalities

6. History or presence of cardiac arrest or unexplained syncope

7. Hypokalemia

8. History of myocardial infarction or severe unstable angina

9. Any medication administered within 2 weeks prior to 1st dose of TAS3681 that is known to prolong the QT interval or be arrhythmogenic

10. 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

11. Serious illness or medical condition that could affect the safety or tolerability of study treatments

12. Received prior treatment with TAS3681

13. User of herbal products

14. Any condition or reason that in the opinion of the investigator, interferes with the ability of the participant to participate in the trial

15. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Taiho Oncology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Univeristy of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Florida Cancer Specialists & Research Institute

Sarasota, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

UMMC-Cancer Center and Research Institute

Jackson, Missouri, United States

GU Research Network / Urology Cancer Center

Omaha, Nebraska, United States

Premier Oncology Group

Edison, New Jersey, United States

MSKCC

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

University of Wisconsin-Carbone Cancer Center

Madison, Wisconsin, United States

Institut Bergonie

Bordeaux, , France

Centre Léon BERARD

Lyon, , France

Hospices Civils de Lyon

Lyon, , France

Institut Paoli Calmettes

Marseille, , France

Institut régional du Cancer de Montpellier - ICM Val d'Aurelle

Montpellier, , France

Centre Antoine Lacassagne

Nice, , France

HEGP- Hôpital Européen Georges Pompidou

Paris, , France

Centre eugenie Marquis

Rennes, , France

Hopital Foch

Suresnes, , France

Gustave Roussy

Villejuif, , France

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Institut Catala d Oncologia - L Hospitalet de Llobregat

Barcelona, , Spain

Hospital Provincial de Castellon

Castellana, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital 12 de Octubre

Madrid, , Spain

Hospital Universitari Parc Taulí

Sabadell, , Spain

Hospital Marques de Valdecilla

Santander, , Spain

Sarah Cannon Research Institute UK

London, England, United Kingdom

The Christie NHS Foundation Trust- The Christie Clinic

Manchester, Greater Manchester, United Kingdom

Royal Marsden Hospital (RMH) NHS Foundation Trust (DDU)

Sutton, Surrey, United Kingdom

Royal Marsden Hospital (RMH) NHS Foundation Trust

Sutton, Surrey, United Kingdom

Cambridge University Hospitals NHS Foundation

Cambridge, , United Kingdom

Countries

United States; France; Spain; United Kingdom

Other Identifiers

2015-002745-55

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TO-TAS3681-101

Identifier Type: -

Identifier Source: org_study_id