A phase 1/2, open-label, multicenter study, designed to evaluate the safety, tolerability, the blood concentration values and efficacy of a substance called TAS0728.
- Registration Number
- EUCTR2017-004415-39-FR
- Lead Sponsor
- Taiho Oncology, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 204
1.Male or females with an age = 18 years.
2.Subjects with histological- or cytological-confirmed, advanced cancer, who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists. Subjects may have received two different forms of specific anti-HER2 therapy for their cancer except for breast cancer where receipt of up to four lines of anti-HER2 therapy is allowed prior to enrollment.
a.For Phase 1, only subjects with the following molecular/genetic alterations will be enrolled:
i.HER2+ determined by local laboratory, for example: immunohistochemistry (IHC) 3+ and/or fluorescence in situ hybridization (FISH)+ by an accurate and validated assay, or potentially actionable HER2 or HER3 mutation or amplification by next generation sequencing.
b.For Phase 2a, subjects with one of the following tumor types will be enrolled as determined by local laboratory:
i.Urothelial cancer with HER2 or HER3 mutation
ii.Biliary tract cancer with HER2 or HER3 mutation
iii.Breast cancer with HER2 or HER3 mutation
iv.Breast cancer with HER2 amplification or overexpression as per ASCO-CAP 2013 guidelines
v.NSCLC with HER2 or HER3 mutation
vi.CRC with HER2 mutation or amplification
vii.Other tumors with HER2 mutation/amplification/overexpression or HER3 mutation (gastric/GEJ, endometrial).
c.For Phase 2a, subjects should also meet the following criteria:
i.Radiological progression on the last line of therapy before entering this trial must be documented
ii.At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
3.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4.Subjects must have the following laboratory values:
a.ANC = 1.5 × 109/L
b.Hemoglobin = 8.0 g/dL
c.Platelet count = 75 × 109/L
d.Albumin = 3 g/dL
e.Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for serum albumin) or ionized calcium within institutional normal limits
f.Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase and alanine aminotransferase/serum glutamic-pyruvic transaminase = 3 × upper limit of normal (ULN) or = 5.0 × ULN if liver metastases are present
g.Total serum bilirubin = 1.5 × ULN
h.Serum creatinine = 1.4 × ULN or 24-hour or calculated creatinine clearance (Ccr) = 50 mL/min (according to Cockcroft Gault formula).* For subjects in Phase 2a with urothelial cancer, a creatinine clearance of = 40 mL/min is acceptable.
5.Left ventricular ejection fraction (LVEF) > institutional lower limit of normal.
*For a calculated Ccr value, the eligibility should be determined using the Cockcroft Gault formula:
Male Ccr (mL/min) = Body weight (kg) × (140 – age)/[72 × serum creatinine (mg/dL)]
Female Ccr (mL/min) = male Ccr × 0.85.
6. 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 must agree to use
Disease exclusions
1.Subjects with a history of brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases. Subjects with treated brain metastases that are asymptomatic and have been clinically stable for at least 4 weeks will be eligible.
Medical condition exclusions
2.Subjects who have a history of another primary malignancy, other than:
a.carcinomas in situ, eg, breast, cervix, and prostate
b.locally excised nonmelanoma skin cancer
c.A subject who has had no evidence of disease from another primary cancer for 2 or more years.
3.Any other clinically significant acute or chronic medical or psychiatric condition or any laboratory abnormality that may increase the risk associated with study drug administration, or may interfere with the interpretation of study results such as, but not limited to:
a.Uncontrolled diabetes mellitus
b.Liver disease such as decompensated liver disease
c.Life-threatening autoimmune disease.
4.Diseases that significantly affect GI absorption of the compound.
5.Subjects who have impaired cardiac function or clinically significant cardiac disease, including any of the following:
a.Baseline corrected QT level using Fridericia formula (QTcF) > 480 ms or congenital QT syndrome
b.History or presence of serious uncontrolled ventricular arrhythmias
c.Any New York Heart Association Classification of Heart Failure = Class II Severe/unstable angina, New York Heart Association classification 4 Congestive Heart Failure (Appendix 1)
d.Echocardiogram or multiple grated acquisition under 50% ejection fraction.
Prior therapy exclusions
6.Chemotherapy, biologic therapy, targeted therapy, immunotherapy, extended-field radiotherapy, or investigational agents within 5 half-lives or within 4 weeks (whichever is shorter) prior to administration of first dose of study drug on Day 1 or have not recovered from the side effects of such therapy.
7.Major surgery/surgical therapy for any cause within 4 weeks of first dose.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method