Advanced Solid Tumors (Excluding Breast Cancer)
Conditions
Keywords
Advanced solid tumors (excluding breast cancer) for which no standard therapy exists
Brief summary
The purpose of this study is to evaluate the cardiac safety of TAS-102 in patients with advanced solid tumors.
Detailed description
This is a Phase 1, nonrandomized study to evaluate the cardiac safety of TAS-102 in patients with advanced solid tumors. The study is conducted in 2 phases: the cardiac safety evaluation phase to investigate cardiac repolarization and the cardiac safety profile (Cycle 1) and the extension phase to assess the safety profile and antitumor activity (subsequent cycles).
Interventions
DRUGTAS-102
35 mg/m2/dose, orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria is met.
DRUGPlacebo
Placebo tablets, orally, single dose.
Sponsors
Taiho Oncology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has provided written informed consent 2. Has advanced solid tumors (excluding breast cancer) for which no standard therapy exists 3. Has received no more than 5 prior cancer therapies 4. ECOG performance status of 0 or 1 5. Is able to take medications orally 6. Corrected QT interval using Bazett's correction is no more than 450 msec on resting ECG 7. Has adequate organ function (bone marrow, kidney and liver) 8. Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control.
Exclusion criteria
1. Has had certain other recent treatment e.g. major surgery, extended field radiation, anticancer therapy, received investigational agent, within the specified time frames prior to study drug administration 2. Certain serious illnesses or medical condition(s) 3. Has a family history of unexplained sudden death or long QT syndrome 4. Has had a documented cardiovascular complication following a fluoropyrimidine-derived treatment 5. Is a patient for whom it is not technically possible to obtain quality ECG tracings 6. Is receiving a concomitant drug that is known to affect QT interval or to be arrhythmogenic 7. Has unresolved toxicity of greater than or equal to CTCAE Grade 2 attributed to any prior therapies 8. Known sensitivity to TAS-102 or its components 9. Is a pregnant or lactating female 10. Refuses to use an adequate means of contraception (including male patients)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| QTc interval | Days -2, -1, 1, and 12 of Cycle 1 | Predose (Day -2) to post-dose changes and absolute values in QTc interval after placebo (Day -1, Cycle 1), after a single dose of TAS-102 (Day 1, Cycle 1), and after multiple doses (Day 12, Cycle 1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantitative and Qualitative ECG parameters | Days -2, -1, 1, and 12 of Cycle 1 | Predose (Day -2) to postdose changes and absolute values in quantitative Holter ECG parameters (heart rate, RR, PR and QRS intervals) after placebo (Day -1, Cycle 1), after a single dose of TAS-102 (Day 1, Cycle 1), and after multiple doses (Day 12, Cycle 1). In addition, qualitative assessments of Holter ECG recordings will be performed. |
| Relationship between TAS-102 pharmacokinetics and its effect on cardiac repolarization | Days 1 and 12 of Cycle 1 | Pharmacokinetic samples are taken on Days 1 and 12 of Cycle 1. The relationship between plasma concentrations of TAS-102 and the change from baseline in QTc adjusted by placebo will be quantified using a linear mixed effect model approach. |
| Safety monitoring including adverse events, vital signs, and laboratory assessments | Through 30 days following last administration of study medication or until initiation of new anticancer treatment | Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) will be used. |
| Tumor assessments using Response Evaluation Criteria in Solid Tumors (RECIST) | Every 8 weeks through Cycle 6 (ie, through 24 weeks). Thereafter, assessments will be performed at least every 12 weeks according to site standard of care, until at least one of the treatment discontinuation criteria is met. | — |
Countries
United States
Outcome results
None listed