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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02566772
Recruitment Status : Active, not recruiting
First Posted : October 2, 2015
Last Update Posted : May 31, 2022
Sponsor:
Information provided by (Responsible Party):
Taiho Oncology, Inc.

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).

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 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.

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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 2022
Estimated Study Completion Date : October 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: TAS3681
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
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.




Primary Outcome Measures :
  1. Number of patients with dose-limiting toxicities [ Time Frame: Through 1 month ]
  2. Escalation Phase: Number of patients with treatment-emergent adverse events and significant ECG abnormalities [ Time Frame: Through 6 months (or until patient discontinuation) ]
    Based on treatment-emergent adverse events, serious adverse events (SAEs), clinical laboratory tests, vital signs, 12-lead electrocardiograms (ECGs)

  3. Expansion Phase: Overall Response Rate (ORR) [ Time Frame: Through 6 months (or until patient discontinuation) ]
    ORR based on investigator-assessed radiographic response per PCWG3/modified RECIST 1.1


Secondary Outcome Measures :
  1. Escalation Phase: Prostate Specific Antigen (PSA) response [ Time Frame: Up to 6 months (or until patient discontinuation) ]
  2. Escalation Phase: Time to PSA progression [ Time Frame: Up to 6 months (or until patient discontinuation) ]
  3. Escalation Phase: Maximum concentration of TAS3681 in plasma [ Time Frame: Through Day 15 in Cycle 1 (each cycle is 28 days) ]
  4. Escalation Phase: Time to reach maximum concentration of TAS3681 [ Time Frame: At Day 15 in Cycle 1 (each cycle is 28 days) ]
  5. Escalation Phase: Area under the concentration-time curve of TAS3681 [ Time Frame: Through Day 15 in Cycle 1 (each cycle is 28 days) ]
  6. Escalation Phase: Terminal half-life time of TAS3681 [ Time Frame: Through Day 15 in Cycle 1 (each cycle is 28 days) ]
  7. Escalation Phase: Accumulation ratio of TAS3681 [ Time Frame: Through Day 15 in Cycle 1 (each cycle is 28 days) ]
  8. 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) ]
  9. Expansion Phase: Prostate Specific Antigen (PSA) response [ Time Frame: Up to 6 months (or until patient discontinuation) ]
  10. Expansion Phase: Number of patients with treatment-emergent adverse events and significant ECG abnormalities [ Time Frame: Through 6 months (or until patient discontinuation) ]
    Based on treatment-emergent adverse events, serious adverse events (SAEs), clinical laboratory tests, vital signs, 12-lead ECGs

  11. Expansion Phase: Maximum concentration of TAS3681 in plasma [ Time Frame: Through Day 15 during Cycle 1 (each cycle is 28 days) ]
  12. Expansion Phase: Time to reach maximum concentration of TAS3681 [ Time Frame: Through Day 15 during Cycle 1 (each cycle is 28 days) ]
  13. Expansion Phase: Area under the concentration-time curve of TAS3681 [ Time Frame: Through Day 15 during Cycle 1 (each cycle is 28 days) ]
  14. Expansion Phase: Terminal half-life time of TAS3681 [ Time Frame: Through Day 15 of Cycle 1 (each cycle is 28 days) ]
  15. 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) ]

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 ]
  3. Severity and impact of pain on daily function using Brief Pain Inventory - Short Form (BPI-SF). [ Time Frame: Through 6 months (or until patient discontinuation) ]


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
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

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 ClinicalTrials.gov identifier (NCT number): NCT02566772


Locations
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Sponsors and Collaborators
Taiho Oncology, Inc.
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Responsible Party: Taiho Oncology, Inc.
ClinicalTrials.gov 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: May 31, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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
Neoplasms
Prostatic Diseases