Study of TAS3681 in Metastatic Castration Resistant Prostate Cancer

NCT02566772 | Completed Phase 1 FDA Drug

• 2 other identifiers: TO-TAS3681-1012015-002745-55
• Study Type: interventional
• Target: 130
• Locations: 4 countries
• Sites: 33

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).

Conditions

Metastatic Castration Resistant Prostate Cancer

Keywords

Prostate Cancer

Outcome Measures

Primary Outcomes (3)

• Number of patients with dose-limiting toxicities

  Through 1 month

• Escalation Phase: Number of patients with treatment-emergent adverse events and significant ECG abnormalities

  Based on treatment-emergent adverse events, serious adverse events (SAEs), clinical laboratory tests, vital signs, 12-lead electrocardiograms (ECGs)

  Through 6 months (or until patient discontinuation)

• Expansion Phase: Overall Response Rate (ORR)

  ORR based on investigator-assessed radiographic response per PCWG3/modified RECIST 1.1

  Through 6 months (or until patient discontinuation)

Secondary Outcomes (15)

• Escalation Phase: Prostate Specific Antigen (PSA) response

  Up to 6 months (or until patient discontinuation)

• Escalation Phase: Time to PSA progression

  Up to 6 months (or until patient discontinuation)

• Escalation Phase: Maximum concentration of TAS3681 in plasma

  Through Day 15 in Cycle 1 (each cycle is 28 days)

• Escalation Phase: Time to reach maximum concentration of TAS3681

  At Day 15 in Cycle 1 (each cycle is 28 days)

• Escalation Phase: Area under the concentration-time curve of TAS3681

  Through Day 15 in Cycle 1 (each cycle is 28 days)

Study Arms (1)

TAS3681

EXPERIMENTAL

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.

Drug: TAS3681

Interventions

TAS3681 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.

TAS3681

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (33)

Univeristy of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Florida Cancer Specialists & Research Institute

Sarasota, Florida, 34232, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

UMMC-Cancer Center and Research Institute

Jackson, Missouri, 39213, United States

Location

GU Research Network / Urology Cancer Center

Omaha, Nebraska, 68130, United States

Location

Premier Oncology Group

Edison, New Jersey, 08837, United States

Location

MSKCC

New York, New York, 10065, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

University of Wisconsin-Carbone Cancer Center

Madison, Wisconsin, 53705, United States

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Léon BERARD

Lyon, 69008, France

Location

Hospices Civils de Lyon

Lyon, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

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

Montpellier, 34298, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

HEGP- Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

Centre eugenie Marquis

Rennes, 35042, France

Location

Hopital Foch

Suresnes, 92151, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Institut Catala d Oncologia - L Hospitalet de Llobregat

Barcelona, 08908, Spain

Location

Hospital Provincial de Castellon

Castellana, 12002, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitari Parc Taulí

Sabadell, 08208, Spain

Location

Hospital Marques de Valdecilla

Santander, 39008, Spain

Location

Sarah Cannon Research Institute UK

London, England, United Kingdom

Location

The Christie NHS Foundation Trust- The Christie Clinic

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

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

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Royal Marsden Hospital (RMH) NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Cambridge University Hospitals NHS Foundation

Cambridge, CB2 0QQ, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2015
• First Posted: October 2, 2015
• Study Start: March 1, 2016
• Primary Completion: August 9, 2022
• Study Completion: April 26, 2024
• Last Updated: September 3, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (7); GB (5); US (11); FR (10)