Study of TAS3681 in Metastatic Castration Resistant Prostate Cancer

Metastatic Castration Resistant Prostate Cancer Clinical Trial

Official title:

A Phase 1, Open-Label, Non-Randomized, Safety, Tolerability and Pharmacokinetic Study of TAS3681 in Patients With Metastatic Castration Resistant Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02566772
• Other study ID #: TO-TAS3681-101
• Secondary ID: 2015-002745-55
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 2016
• Est. completion date: March 2024

Study information

• Verified date: December 2023
• Source: Taiho Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: March 2024
• Est. primary completion date: August 9, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic Castration Resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
France	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 Cedex
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Institut Catala d Oncologia - L Hospitalet de Llobregat	Barcelona
Spain	Hospital Provincial de Castellon	Castellana
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitari Parc Taulí	Sabadell
Spain	Hospital Marques de Valdecilla	Santander
United Kingdom	Cambridge University Hospitals NHS Foundation	Cambridge
United Kingdom	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	Sutton	Surrey
United Kingdom	Royal Marsden Hospital (RMH) NHS Foundation Trust (DDU)	Sutton	Surrey
United States	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	Premier Oncology Group	Edison	New Jersey
United States	UMMC-Cancer Center and Research Institute	Jackson	Missouri
United States	University of Wisconsin-Carbone Cancer Center	Madison	Wisconsin
United States	MSKCC	New York	New York
United States	GU Research Network / Urology Cancer Center	Omaha	Nebraska
United States	Univeristy of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Florida Cancer Specialists & Research Institute	Sarasota	Florida
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Taiho Oncology, Inc.

Countries where clinical trial is conducted

United States,  France,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with dose-limiting toxicities		Through 1 month
Primary	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)
Primary	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	Escalation Phase: Prostate Specific Antigen (PSA) response		Up to 6 months (or until patient discontinuation)
Secondary	Escalation Phase: Time to PSA progression		Up to 6 months (or until patient discontinuation)
Secondary	Escalation Phase: Maximum concentration of TAS3681 in plasma		Through Day 15 in Cycle 1 (each cycle is 28 days)
Secondary	Escalation Phase: Time to reach maximum concentration of TAS3681		At Day 15 in Cycle 1 (each cycle is 28 days)
Secondary	Escalation Phase: Area under the concentration-time curve of TAS3681		Through Day 15 in Cycle 1 (each cycle is 28 days)
Secondary	Escalation Phase: Terminal half-life time of TAS3681		Through Day 15 in Cycle 1 (each cycle is 28 days)
Secondary	Escalation Phase: Accumulation ratio of TAS3681		Through Day 15 in Cycle 1 (each cycle is 28 days)
Secondary	Escalation Phase: Tumor response per PCWG3/RECIST 1.1 including ORR, and duration of response (DOR)		Through 6 months ( or until patient discontinuation)
Secondary	Expansion Phase: Prostate Specific Antigen (PSA) response		Up to 6 months (or until patient discontinuation)
Secondary	Expansion 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 ECGs	Through 6 months (or until patient discontinuation)
Secondary	Expansion Phase: Maximum concentration of TAS3681 in plasma		Through Day 15 during Cycle 1 (each cycle is 28 days)
Secondary	Expansion Phase: Time to reach maximum concentration of TAS3681		Through Day 15 during Cycle 1 (each cycle is 28 days)
Secondary	Expansion Phase: Area under the concentration-time curve of TAS3681		Through Day 15 during Cycle 1 (each cycle is 28 days)
Secondary	Expansion Phase: Terminal half-life time of TAS3681		Through Day 15 of Cycle 1 (each cycle is 28 days)
Secondary	Expansion:Tumor response measures including duration of response (DOR), radiologic progression-free survival (rPFS), overall survival (OS), clinical benefit rate (CBR; percentage of participants with complete response, partial response or stable disease)		Through 6 months (or until patient discontinuation)