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Study of TAS3681 in Metastatic Castration Resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02566772
Recruitment Status : Recruiting
First Posted : October 2, 2015
Last Update Posted : November 1, 2019
Information provided by (Responsible Party):
Taiho Oncology, Inc.

Brief Summary:
The purpose of this trial is to investigate the safety and tolerability of TAS3681 and to find the maximum tolerated dose of TAS3681.

Condition or disease Intervention/treatment Phase
Metastatic Castration Resistant Prostate Cancer Drug: TAS3681 Phase 1

Detailed Description:

This is a first in human, multinational, phase 1, open-label study of TAS3681 in patients with metastatic castration resistant prostate cancer (mCRPC)evaluating safety, tolerability, pharmacokinetics and preliminary antitumor activity in patients with mCRPC for which there is no standard therapy. Eligible patients will either be enrolled in the dose escalation phase to evaluate safety and determine the maximum tolerated dose for TAS3681, including a preliminary evaluation of food effect, or the expansion phase in which additional cohorts of patients may be enrolled to further evaluate safety and preliminary efficacy of TAS3681 at the MTD or at a lower dose.

Approximately 100 evaluable patients will be enrolled in the Dose Escalation Phase and approximately 100 patients will be enrolled in the Expansion Phase.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Non-Randomized, Safety, Tolerability and Pharmacokinetic Study of TAS3681 in Patients With Metastatic Castration Resistant Prostate Cancer
Actual Study Start Date : March 2016
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: TAS3681
All patients will receive TAS3681 in 28 day cycles,. The study will enroll patients who have progressed after abiraterone or enzalutamide (expansion phase) and those who have progressed after abiraterone, enzalutamide and chemotherapy (dose escalation phase). - Number of cycles: approximately 6 or until discontinuation criteria is met. Eleven dose escalation cohorts are planned, one of which will include preliminary assessment of food effect. The MTD/recommended dose for further development will be used for patients in the expansion phase.
Drug: TAS3681
TAS3681 will be provided as 25 mg and 100 mg tablets to be administered orally for 28 day cycles, Number of cycles: approximately 6 or until discontinuation criteria is met.

Primary Outcome Measures :
  1. Number of participants with dose limiting toxicity [ Time Frame: Through 1 month ]
  2. Number of patients with adverse events and significant ECG abnormalities [ Time Frame: through 6 months (or until patient discontinuation) ]

Secondary Outcome Measures :
  1. Prostate Specific Antigen (PSA) response [ Time Frame: Up to 6 months (or until patient discontinuation) ]
  2. Maximum concentration of TAS3681 in plasma [ Time Frame: At Day 15 in Cycle 1 (each cycle is 28 days) ]
  3. Time to reach maximum concentration of TAS3681 [ Time Frame: At Day 15 in Cycle 1 (each cycle is 28 days) ]
  4. Area under the concentration-time curve of TAS3681 [ Time Frame: At Day 15 in Cycle 1 (each cycle is 28 days) ]
  5. Terminal half-life time of TAS3681 [ Time Frame: At Day 15 in Cycle 1 (each cycle is 28 days) ]
  6. Accumulation ratio of TAS3681 [ Time Frame: At Day 15 in Cycle 1 (each cycle is 28 days) ]
  7. Tumor response as per RECIST 1.1 and PCWG3 [ Time Frame: Through 6 months ( or until patient discontinuation) ]

Other Outcome Measures:
  1. Change from baseline in Circulating Tumor Cell (CTC) number in blood [ Time Frame: Baseline, end of week 4, at the end of every 12 weeks, and end of every 12 weeks through study completion, an average of 6 months ]
  2. Number of patients with AR-v7 positivity in circulating tumor cells [ Time Frame: Baseline ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male > 18 years of age
  2. Histological or cytological evidence of metastatic castrate resistant prostate cancer with progression defined in PCWG3; Scher HI 2015 intolerance of standard chemotherapy
  3. ECOG performance status of < 1 on Day1 Cycle 1
  4. Ongoing androgen deprivation with serum testosterone < 50 ng/dl
  5. Ability to take medication orally
  6. Adequate organ function
  7. Willing to comply with scheduled visits and procedures

Exclusion Criteria:

  1. QTc > 450ms, 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 cardia arrest or unexplained syncope
  7. Hypokalemia
  8. History of myocardial infarction or severe unstable angina
  9. Any medication administered within 4 weeks prior to 1st dose of TAS3681 that is known to affect QT interval or arrhythmogenic
  10. Serious illness or medical condition that could affect the safety or tolerability of study treatments
  11. Received prior treatment of TAS3681
  12. User of herbal products
  13. Any condition or reason that in the opinion of the investigator, interferes with the ability of the patient to participate in the trial.
  14. To be eligible to participate in the food effect assessment, patients 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02566772

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Contact: Elizabeth Calleja, MD +1-609-285-5280

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United States, California
Univeristy of California Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
United States, Florida
Sarah Cannon Research Institute Recruiting
Sarasota, Florida, United States, 34232
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Washington
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
United Kingdom
The Christie Clinic Recruiting
Manchester, Greater Manchester, United Kingdom, M20 4BX
Institute of Cancer Research Recruiting
Sutton, Surrey, United Kingdom, SM2 5NG
Sponsors and Collaborators
Taiho Oncology, Inc.
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Responsible Party: Taiho Oncology, Inc. Identifier: NCT02566772    
Other Study ID Numbers: TO-TAS3681-101
2015-002745-55 ( EudraCT Number )
First Posted: October 2, 2015    Key Record Dates
Last Update Posted: November 1, 2019
Last Verified: October 2019
Keywords provided by Taiho Oncology, Inc.:
Prostate Cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases