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Study of TAS3681 in Metastatic Castration Resistant Prostate Cancer

Sponsor
Taiho Oncology, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02566772
Collaborator
(none)
200
Enrollment
39
Locations
1
Arm
79
Anticipated Duration (Months)
5.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Anticipated 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 :
Mar 1, 2016
Anticipated Primary Completion Date :
Sep 1, 2022
Anticipated Study Completion Date :
Oct 1, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Number of patients with dose-limiting toxicities [Through 1 month]

  2. Escalation Phase: Number of patients with treatment-emergent adverse events and significant ECG abnormalities [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) [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 [Up to 6 months (or until patient discontinuation)]

  2. Escalation Phase: Time to PSA progression [Up to 6 months (or until patient discontinuation)]

  3. Escalation Phase: Maximum concentration of TAS3681 in plasma [Through Day 15 in Cycle 1 (each cycle is 28 days)]

  4. Escalation Phase: Time to reach maximum concentration of TAS3681 [At Day 15 in Cycle 1 (each cycle is 28 days)]

  5. Escalation Phase: Area under the concentration-time curve of TAS3681 [Through Day 15 in Cycle 1 (each cycle is 28 days)]

  6. Escalation Phase: Terminal half-life time of TAS3681 [Through Day 15 in Cycle 1 (each cycle is 28 days)]

  7. Escalation Phase: Accumulation ratio of TAS3681 [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) [Through 6 months ( or until patient discontinuation)]

  9. Expansion Phase: Prostate Specific Antigen (PSA) response [Up to 6 months (or until patient discontinuation)]

  10. Expansion Phase: Number of patients with treatment-emergent adverse events and significant ECG abnormalities [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 [Through Day 15 during Cycle 1 (each cycle is 28 days)]

  12. Expansion Phase: Time to reach maximum concentration of TAS3681 [Through Day 15 during Cycle 1 (each cycle is 28 days)]

  13. Expansion Phase: Area under the concentration-time curve of TAS3681 [Through Day 15 during Cycle 1 (each cycle is 28 days)]

  14. Expansion Phase: Terminal half-life time of TAS3681 [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) [Through 6 months (or until patient discontinuation)]

Other Outcome Measures

  1. Change from baseline in Circulating Tumor Cell (CTC) number in blood [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 [Baseline]

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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
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 (excluding neuroendocrine differentiation and small cell histology) who are castration resistant and have:

  3. Dose escalation: documented progression defined in PCWG3 and/or intolerance to abiraterone and/or enzalutamide therapy, as well as 1 or more chemotherapies.

  4. Expansion:

  1. Group A: documented progression after abiraterone or enzalutamide and chemotherapy consisting of no more than 2 prior taxane-based therapies

  1. Group B: documented progression after only abiraterone or enzalutamide therapy without any chemotherapy

  2. Measurable disease per RECIST 1.1 and/or bone metastases

  1. ECOG performance status of ≤1 on Day 1 Cycle 1

  2. Ongoing androgen deprivation with serum testosterone <50 ng/dL

  3. Expansion Phase only: willingness to undergo baseline core biopsies, if feasible

  4. Ability to take medication orally

  5. Adequate organ function

  6. Agree to use effective contraception during the study and for 30 days after the last dose of TAS3681

  7. 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Univeristy of California Davis Comprehensive Cancer Center Sacramento California United States 95817
2 Yale University New Haven Connecticut United States 06520-8028
3 Florida Cancer Specialists & Research Institute Sarasota Florida United States 34232
4 Moffitt Cancer Center Tampa Florida United States 33612
5 University of Maryland Greenebaum Cancer Center Baltimore Maryland United States 21201
6 UMMC-Cancer Center and Research Institute Jackson Missouri United States 39213
7 GU Research Network / Urology Cancer Center Omaha Nebraska United States 68130
8 Premier Oncology Group Edison New Jersey United States 08837
9 Montefiore Medical Center Bronx New York United States 10461
10 Memorial Sloan Kettering Cancer Center New York New York United States 10065
11 Associated Medical Professionals of NY, PLLC Syracuse New York United States
12 Seattle Cancer Care Alliance Seattle Washington United States 98109
13 University of Wisconsin-Carbone Cancer Center Madison Wisconsin United States 53705
14 Cliniques Universitaires Saint-Luc Brussels Belgium 1200
15 Institut Jules Bordet Brussel Belgium 1000
16 Institut Bergonie Bordeaux France 33076
17 Centre Jean Perrin Clermont Ferrand France 63011
18 Centre Léon BERARD Lyon France 69008
19 Hospices Civils de Lyon Lyon France
20 Institut Paoli Calmettes Marseille France 13273
21 Institut régional du Cancer de Montpellier - ICM Val d'Aurelle Montpellier France 34298
22 Centre Antoine Lacassagne Nice France 06189
23 HEGP- Hôpital Européen Georges Pompidou Paris France 75015
24 Centre eugenie Marquis Rennes France 35042
25 Hopital Foch Suresnes France 92151
26 Gustave Roussy Villejuif Cedex France 94805
27 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
28 Institut Catala d Oncologia - L Hospitalet de Llobregat Barcelona Spain 08908
29 Hospital Provincial de Castellon Castellana Spain 12002
30 Hospital Universitario Ramon y Cajal Madrid Spain 28034
31 Hospital 12 de Octubre Madrid Spain 28041
32 Hospital Universitari Parc Taulí Sabadell Spain 08208
33 Hospital Marques de Valdecilla Santander Spain 39008
34 Sarah Cannon Research Institute UK London England United Kingdom
35 The Christie NHS Foundation Trust- The Christie Clinic Manchester Greater Manchester United Kingdom M20 4BX
36 Royal Marsden Hospital (RMH) NHS Foundation Trust Sutton Surrey United Kingdom SM2 5NG
37 Royal Marsden Hospital (RMH) NHS Foundation Trust (DDU) Sutton Surrey United Kingdom SM2 5PT
38 Cambridge University Hospitals NHS Foundation Cambridge United Kingdom CB2 0QQ
39 University of Glasgow - Institute of Cancer Sciences; Glasgow United Kingdom G12 8QQ

Sponsors and Collaborators

  • Taiho Oncology, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Taiho Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT02566772
Other Study ID Numbers:
  • TO-TAS3681-101
  • 2015-002745-55
First Posted:
Oct 2, 2015
Last Update Posted:
May 31, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
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:
Prostatic Neoplasms

Study Results

No Results Posted as of May 31, 2022