oncology solid tumors
Conditions
Interventions
TAS-119 Dose Escalation:
TAS-119 will be given PO, BID, without food (ie, for at least 1 hour before or
2 hours after the morning and evening meal) during Days 1-4, Days 8-
11, and Days 15-18) of ea
for each dose level, the second and third patients will be enrolled * 7 days
after the 1st patient started dosing. Once patients have received treatment at
any given dose level, escalation to subseq
no transition of patients between assigned dose
levels will be allowed.
The TAS-119 MTD will be defined as the highest dose level at which < 33% of the
patients in the dose level experience a dosel
Sponsors
Taiho Oncology Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: The Subject: 1. Is a male or female, * 18 years of age, who has provided written informed consent. 2. Has histologically or cytologically confirmed advanced, unresectable and/or metastatic solid tumour(s) for which the patient has no available therapy likely to provide clinical benefit; 3. Has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 on Cycle 1, Day 1. 4. Must have an archival formalin-fixed, paraffin-embedded (FFPE) tumour sample available, to be provided to the Sponsor upon request. 5. In the Expansion Phase: patients should be willing to undergo core tumour biopsy procedure (on or before Day 1, Cycle 1) and on Day 4, Cycle 1 (6 hours ± 2 hours postdose) if, in the judgment of the investigator, it is considered clinically safe and appropriate to do so. This requirement is optional but preferred for patients in Dose Escalation. 6. Should be willing to undergo pretreatment sampling of non-tumour surrogate tissue for pharmacodynamic assessments (ie, a 3 mm punch biopsy of skin from either the arm or the back of the scalp) if, in the judgment of the investigator, it is considered clinically safe and appropriate to do so. 7. Is able to take medications orally (eg, no feeding tube). 8. Has adequate organ function as defined by the following criteria: i. Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT/serum glutamic pyruvic transaminase [SGPT]) * 3.0 × upper limit of normal (ULN). ii. Total serum bilirubin within normal limits. Patients with Gilbert's Syndrome could be considered eligible if bilirubin is * 1 × ULN, but serum bilirubin ratio of unconjugated/conjugated is greater than 1 or most of serum bilirubin fraction should be unconjugated. iii. Absolute neutrophil count of * 1,500/mm3 (ie, * 1.5 × 109/L by International Units [IU]). iv. Platelet count * 100,000/mm3 (IU: * 100 × 109/L). Transfusion of whole blood, platelets, or red blood cells (RBCs) is prohibited within 1 month prior to initiation of study treatment. v. Hemoglobin value of * 9.0 g/dL. vi. Total serum creatinine of * 1.5 × ULN. vii. Serum albumin * 2.5 g/dL. 9. Women of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days prior to starting the study drug. Both males and females and must agree to use effective birth control during the study [prior to the first dose and for 6 months after the last dose if conception is possible during this interval] if conception is possible during this interval. Female patients are considered to not be of childbearing potential if they have a history of tubal ligation or hysterectomy or are post-menopausal with a minimum of 1 year without menses. 10. Is willing and able to comply with scheduled visits and study procedures.
Exclusion criteria
Exclusion criteria: The Subject: 1. Has received prior treatment with TAS-119. 2. Has received treatment with any of the following within the specified time frame prior to study drug administration: a) Major surgery within prior 4 weeks (the surgical incision should be fully healed prior to study drug administration). b) Radiotherapy for extended field within 4 weeks prior to study drug administration or limited field radiotherapy within 2 weeks prior to study drug administration. c) Previous cytotoxic chemotherapy for advanced or metastatic solid tumors consisting of more than 5 different regimens in total. d) Any anticancer therapy within 3 weeks prior to study drug administration (mitomycin within prior 5 weeks). Patients with metastatic prostate cancer receiving luteinizing hormone-releasing (LHRH) analogs will be eligible. e) Any investigational agent received either concurrently or within the last 30 days. f) Transfusion of whole blood, platelets, or packed red blood cells is prohibited within 1 month prior to study treatment. 3. Has a serious illness or medical condition(s) including, but not limited to, the following: a) Known brain metastasis unless the lesions have been previously treated with surgery or radiotherapy, and have been stable off steroids for * 2 months. b) Known leptomeningeal metastasis. c) Known acute systemic infection. d) Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV within the previous 6 months ( if > 6 months cardiac function must be within normal limits [ie, known ejection fraction * 50%] and the patient must be free of cardiac-related symptoms). e) Chronic nausea, vomiting, or diarrhoea, considered to be clinically significant in the opinion of the Investigator. f) Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or a history of serum positivity to hepatitis B or C. g) Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study. 4. Has known hypersensitivity to TAS-119 or any of its components; 5. Is pregnant or lactating female.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Outcome: Identify the maximum tolerated dose (MTD) and the RP2D (200 mg BID) of TAS-119. | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety: * Evaluate the feasibility and tolerability of TAS-119 in the treatment of advanced solid tumours; Efficacy outcomes (Radiological assessments of solid tumours will be performed throughout the study period and analysed using Response Evaluation Criteria inSolid Tumours (RECIST): * Evaluate the preliminary antitumour activity of the RP2D for TAS-119 in the treatment of advanced solid tumours; PK criteria: * Assess the pharmacokinetic (PK) characteristics of TAS-119; Exploratory: * Assess Phospho-HH3 (Ser 10) and mRNA expression of BORA, SGOL2, KIF20A and DEPDC-1 as potential pharmacodynamic biomarkers for TAS-119; * Investigate the myc oncogene as well as beta catenin mutation as a predictive biomarker for TAS 119. * Investigate the relationship between genetic polymorphisms of SLCO1B1 and PK of TAS-119. * Optionally, investigate the presence or absence of circulating tumour cells in peripheral blood as a biomarker to evaluate the response to TAS- 119 treatment (prior to treatment, during treatment, and at progression). | — |
Countries
Netherlands
Outcome results
None listed