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).
Brief Title
Study of TAS3681 in Metastatic Castration Resistant Prostate Cancer
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Metastatic Castration Resistant Prostate Cancer
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
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
Inclusion 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
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
Gender
Male
Gender Based
false
Keywords
Prostate Cancer
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02566772
Org Class
Industry
Org Full Name
Taiho Oncology, Inc.
Org Study Id
TO-TAS3681-101
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 1, Open-Label, Non-Randomized, Safety, Tolerability and Pharmacokinetic Study of TAS3681 in Patients With Metastatic Castration Resistant Prostate Cancer
Primary Outcomes
Outcome Measure
Number of patients with dose-limiting toxicities
Outcome Time Frame
Through 1 month
Outcome Description
Based on treatment-emergent adverse events, serious adverse events (SAEs), clinical laboratory tests, vital signs, 12-lead electrocardiograms (ECGs)
Outcome Measure
Escalation Phase: Number of patients with treatment-emergent adverse events and significant ECG abnormalities
Outcome Time Frame
Through 6 months (or until patient discontinuation)
Outcome Description
ORR based on investigator-assessed radiographic response per PCWG3/modified RECIST 1.1
Outcome Measure
Expansion Phase: Overall Response Rate (ORR)
Outcome Time Frame
Through 6 months (or until patient discontinuation)
Secondary Ids
Secondary Id
2015-002745-55
Secondary Outcomes
Outcome Time Frame
Up to 6 months (or until patient discontinuation)
Outcome Measure
Escalation Phase: Prostate Specific Antigen (PSA) response
Outcome Time Frame
Up to 6 months (or until patient discontinuation)
Outcome Measure
Escalation Phase: Time to PSA progression
Outcome Time Frame
Through Day 15 in Cycle 1 (each cycle is 28 days)
Outcome Measure
Escalation Phase: Maximum concentration of TAS3681 in plasma
Outcome Time Frame
At Day 15 in Cycle 1 (each cycle is 28 days)
Outcome Measure
Escalation Phase: Time to reach maximum concentration of TAS3681
Outcome Time Frame
Through Day 15 in Cycle 1 (each cycle is 28 days)
Outcome Measure
Escalation Phase: Area under the concentration-time curve of TAS3681
Outcome Time Frame
Through Day 15 in Cycle 1 (each cycle is 28 days)
Outcome Measure
Escalation Phase: Terminal half-life time of TAS3681
Outcome Time Frame
Through Day 15 in Cycle 1 (each cycle is 28 days)
Outcome Measure
Escalation Phase: Accumulation ratio of TAS3681
Outcome Time Frame
Through 6 months ( or until patient discontinuation)
Outcome Measure
Escalation Phase: Tumor response per PCWG3/RECIST 1.1 including ORR, and duration of response (DOR)
Outcome Time Frame
Up to 6 months (or until patient discontinuation)
Outcome Measure
Expansion Phase: Prostate Specific Antigen (PSA) response
Outcome Description
Based on treatment-emergent adverse events, serious adverse events (SAEs), clinical laboratory tests, vital signs, 12-lead ECGs
Outcome Time Frame
Through 6 months (or until patient discontinuation)
Outcome Measure
Expansion Phase: Number of patients with treatment-emergent adverse events and significant ECG abnormalities
Outcome Time Frame
Through Day 15 during Cycle 1 (each cycle is 28 days)
Outcome Measure
Expansion Phase: Maximum concentration of TAS3681 in plasma
Outcome Time Frame
Through Day 15 during Cycle 1 (each cycle is 28 days)
Outcome Measure
Expansion Phase: Time to reach maximum concentration of TAS3681
Outcome Time Frame
Through Day 15 during Cycle 1 (each cycle is 28 days)
Outcome Measure
Expansion Phase: Area under the concentration-time curve of TAS3681
Outcome Time Frame
Through Day 15 of Cycle 1 (each cycle is 28 days)
Outcome Measure
Expansion Phase: Terminal half-life time of TAS3681
Outcome Time Frame
Through 6 months (or until patient discontinuation)
Outcome 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)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404