Clinical trial NCT02566772: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Castration Resistant Prostate Cancer
Keywords: Prostate Cancer
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2015-10-02
Enrollment: 130
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

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

Primary outcomes:
measure: Number of patients with dose-limiting toxicities
timeFrame: Through 1 month
measure: Escalation Phase: Number of patients with treatment-emergent adverse events and significant ECG abnormalities
timeFrame: Through 6 months (or until patient discontinuation)
measure: Expansion Phase: Overall Response Rate (ORR)
timeFrame: Through 6 months (or until patient discontinuation)
Secondary outcomes:
measure: Escalation Phase: Prostate Specific Antigen (PSA) response
timeFrame: Up to 6 months (or until patient discontinuation)
measure: Escalation Phase: Time to PSA progression
timeFrame: Up to 6 months (or until patient discontinuation)
measure: Escalation Phase: Maximum concentration of TAS3681 in plasma
timeFrame: Through Day 15 in Cycle 1 (each cycle is 28 days)
measure: Escalation Phase: Time to reach maximum concentration of TAS3681
timeFrame: At Day 15 in Cycle 1 (each cycle is 28 days)
measure: Escalation Phase: Area under the concentration-time curve of TAS3681
timeFrame: Through Day 15 in Cycle 1 (each cycle is 28 days)
measure: Escalation Phase: Terminal half-life time of TAS3681
timeFrame: Through Day 15 in Cycle 1 (each cycle is 28 days)
measure: Escalation Phase: Accumulation ratio of TAS3681
timeFrame: Through Day 15 in Cycle 1 (each cycle is 28 days)
measure: Escalation Phase: Tumor response per PCWG3/RECIST 1.1 including ORR, and duration of response (DOR)
timeFrame: Through 6 months ( or until patient discontinuation)
measure: Expansion Phase: Prostate Specific Antigen (PSA) response
timeFrame: Up to 6 months (or until patient discontinuation)
measure: Expansion Phase: Number of patients with treatment-emergent adverse events and significant ECG abnormalities
timeFrame: Through 6 months (or until patient discontinuation)
measure: Expansion Phase: Maximum concentration of TAS3681 in plasma
timeFrame: Through Day 15 during Cycle 1 (each cycle is 28 days)
measure: Expansion Phase: Time to reach maximum concentration of TAS3681
timeFrame: Through Day 15 during Cycle 1 (each cycle is 28 days)
measure: Expansion Phase: Area under the concentration-time curve of TAS3681
timeFrame: Through Day 15 during Cycle 1 (each cycle is 28 days)
measure: Expansion Phase: Terminal half-life time of TAS3681
timeFrame: Through Day 15 of Cycle 1 (each cycle is 28 days)
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)
timeFrame: Through 6 months (or until patient discontinuation)
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Univeristy of California Davis Comprehensive Cancer Center
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists & Research Institute
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Jackson
country: United States
facility: UMMC-Cancer Center and Research Institute
state: Missouri
city: Omaha
country: United States
facility: GU Research Network / Urology Cancer Center
state: Nebraska
city: Edison
country: United States
facility: Premier Oncology Group
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: MSKCC
state: New York
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Madison
country: United States
facility: University of Wisconsin-Carbone Cancer Center
state: Wisconsin
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Léon BERARD
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Institut régional du Cancer de Montpellier - ICM Val d'Aurelle
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: HEGP- Hôpital Européen Georges Pompidou
city: Rennes
country: France
facility: Centre eugenie Marquis
city: Suresnes
country: France
facility: Hopital Foch
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Catala d Oncologia - L Hospitalet de Llobregat
city: Castellana
country: Spain
facility: Hospital Provincial de Castellon
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Sabadell
country: Spain
facility: Hospital Universitari Parc Taulí
city: Santander
country: Spain
facility: Hospital Marques de Valdecilla
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
state: England
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust- The Christie Clinic
state: Greater Manchester
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital (RMH) NHS Foundation Trust (DDU)
state: Surrey
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital (RMH) NHS Foundation Trust
state: Surrey
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation
Study officials:
References: