Description:
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).
Title
- Brief Title: Study of TAS3681 in Metastatic Castration Resistant Prostate Cancer
- 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 IDs
- ORG STUDY ID:
TO-TAS3681-101
- SECONDARY ID:
2015-002745-55
- NCT ID:
NCT02566772
Conditions
- Metastatic Castration Resistant Prostate Cancer
Interventions
Drug | Synonyms | Arms |
---|
TAS3681 | | TAS3681 |
Purpose
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 open), and will enroll up to approximately 200 patients.
Trial Arms
Name | Type | Description | Interventions |
---|
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. | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Male |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of patients with dose-limiting toxicities |
Time Frame: | Through 1 month |
Safety Issue: | |
Description: | Based on treatment-emergent adverse events, serious adverse events (SAEs), clinical laboratory tests, vital signs, 12-lead electrocardiograms (ECGs) |
Secondary Outcome Measures
Measure: | Escalation Phase: Prostate Specific Antigen (PSA) response |
Time Frame: | Up to 6 months (or until patient discontinuation) |
Safety Issue: | |
Description: | |
Measure: | Escalation Phase: Time to PSA progression |
Time Frame: | Up to 6 months (or until patient discontinuation) |
Safety Issue: | |
Description: | |
Measure: | Escalation Phase: Maximum concentration of TAS3681 in plasma |
Time Frame: | Through Day 15 in Cycle 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Escalation Phase: Time to reach maximum concentration of TAS3681 |
Time Frame: | At Day 15 in Cycle 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Escalation Phase: Area under the concentration-time curve of TAS3681 |
Time Frame: | Through Day 15 in Cycle 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Escalation Phase: Terminal half-life time of TAS3681 |
Time Frame: | Through Day 15 in Cycle 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Escalation Phase: Accumulation ratio of TAS3681 |
Time Frame: | Through Day 15 in Cycle 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Escalation Phase: Tumor response per PCWG3/RECIST 1.1 including ORR, and duration of response (DOR) |
Time Frame: | Through 6 months ( or until patient discontinuation) |
Safety Issue: | |
Description: | |
Measure: | Expansion Phase: Prostate Specific Antigen (PSA) response |
Time Frame: | Up to 6 months (or until patient discontinuation) |
Safety Issue: | |
Description: | |
Measure: | Expansion Phase: Number of patients with treatment-emergent adverse events and significant ECG abnormalities |
Time Frame: | Through 6 months (or until patient discontinuation) |
Safety Issue: | |
Description: | Based on treatment-emergent adverse events, serious adverse events (SAEs), clinical laboratory tests, vital signs, 12-lead ECGs |
Measure: | Expansion Phase: Maximum concentration of TAS3681 in plasma |
Time Frame: | Through Day 15 during Cycle 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Expansion Phase: Time to reach maximum concentration of TAS3681 |
Time Frame: | Through Day 15 during Cycle 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Expansion Phase: Area under the concentration-time curve of TAS3681 |
Time Frame: | Through Day 15 during Cycle 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Expansion Phase: Terminal half-life time of TAS3681 |
Time Frame: | Through Day 15 of Cycle 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | 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) |
Time Frame: | Through 6 months (or until patient discontinuation) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Taiho Oncology, Inc. |
Trial Keywords
Last Updated
May 10, 2021