Clinical trial NCT02965885: A Study of TAS-116 in Patients With Solid Tumors
Official title: A Phase IA/IB Study Evaluating TAS-116 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Phase I
Solid Tumors
Pharmacokinetics
Pharmacodynamics
MTD
TAS116
HSP90 Inhibitor
Neoplasms
HER2 positive MBC
NSCLC EGFR
NSCLC ALK positive
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2016-11-17
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A First-in-Human (FIH) study of TAS-116 in patients with advanced solid tumors was first initiated in Japan in April 2014 and has been ongoing since then. The study consists of a dose escalation phase and a dose expansion phase. Three dosing regimens of TAS-116, once daily (QD), every other day (QOD) and 5 days on/2 days off regimens in 21-day cycles, are being evaluated. This phase I study is also planned to enroll patients with advanced solid tumors in UK to confirm the MTD, safety, tolerability, and pharmacokinetics of TAS-116 in a Western patient population in the dose expansion phase. In addition, patients with HER2+ MBC, NSCLC harboring EGFR mutations or NSCLC harbouring ALK translocations will be further evaluated for safety, tolerability, and efficacy in 3 separate cohorts at recommended dose of TAS-116 on the 5 days on/2 days off regimen.


Eligibility criteria: Inclusion Criteria:

1. Male or females with an age ≥ 18 years (≥ 20 years in Japan)
2. Patients with histological- or cytological-confirmed, advanced unresectable breast, gastric, or non-small cell lung cancer, who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists.

   a. Part C: Only the following subtype of tumors with the molecular/genetic alterations will be enrolled: HER2 positive MBC Advanced NSCLC, harboring EGFR mutations after progression on osimertinib Advanced NSCLC, harboring ALK translocations after treatment with alectinib or at least 2 ALK inhibitors
3. Has At least one measurable lesion as defined by RECIST criteria
4. Is able to take medications orally (e.g., no feeding tube).
5. Is able to agree to and sign informed consent and to comply with the protocol
6. Has adequate organ function

Exclusion Criteria:

1. Has a serious illness or medical condition(s)
2. Has received treatment with any prescribed treatments within specified time frames prior to study drug administration
3. Significant ophthalmologic abnormality,
4. Impaired cardiac function or clinically significant cardiac disease

Primary outcomes:
measure: Number of patients experiencing Dose Limiting Toxicity graded according to CTCAE Version 4.03, observed in the Cycle 1 in order to meet the objective of assessment of the MTD of TAS-116 (Part A)
timeFrame: 21 days in Cycle 1
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Parts A, B and C)
timeFrame: Safety monitoring will begin at the informed consent obtained and continue up to 28 days after the last dose of TAS-116 or until new anti-tumor therapy, whichever is earlier.
measure: Objective Response Rate using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) (Part C)
timeFrame: Up to 2 Years
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) after administration of TAS-116 (Parts A and B)
timeFrame: 21 days in Cycle 1
measure: Area under the plasma drug concentration-time curve (AUC) after administration of TAS-116 (Parts A and B)
timeFrame: 21 days in Cycle 1
measure: Disease Control Rate using RECIST 1.1 (Parts A, B, and C)
timeFrame: Up to last participant completes at least 6 months
measure: Duration of Response (Part C)
timeFrame: Up to last participant completes at least 6 months
measure: Progression Free Survival (Part C)
timeFrame: Up to last participant completes at least 6 months
measure: Overall Survival
timeFrame: Up to last participant completes at least 6 months
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Greenville
country: United States
facility: Greenville Health System, Institute for Translational Oncology Research
state: South Carolina
city: Fairfax
country: United States
facility: US Oncology - Virginia Cancer Specialists, P.C.
state: Virginia
city: Bologna
country: Italy
facility: Policlinico S.Orsola-Malpighi, U.O. Oncologia Medica
city: Catania
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico-Vittorio Emanuele Oncologia Medica
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia , Sviluppo di Nuovi Farmaci per Terapie Innovative
city: Roma
country: Italy
facility: Regina Elena National Cancer Institute
city: Newcastle Upon Tyne
country: United Kingdom
facility: Northern Centre for Cancer Care
state: England
city: London
country: United Kingdom
facility: Division of Cancer Studies, Kings College London
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust Institute of Cancer Sciences, University of Manchester
city: Sutton
country: United Kingdom
facility: Royal Marsden
Study officials:
References: