A Safety, Tolerability and Pharmacokinetic Study of TAS-114 in Combination With Capecitabine in Patients With Advanced Solid Tumors

A Phase 1, Open-Label, Non-randomized, Dose-Escalating Safety, Tolerability, and Pharmacokinetic Study of TAS-114 in Combination With Capecitabine in Patients With Advanced Solid Tumors

The purpose of this exploratory study is to investigate the safety and determine the maximum tolerated dose (MTD) of TAS-114 in combination with capecitabine in patients with advanced solid tumors for which the patients have no available therapy likely to convey clinical benefit.

In animal models, co-administration of TAS 114 and capecitabine has shown antitumor effects exceeding the maximum efficacy obtained by capecitabine alone. Developing a novel chemotherapy based on the combined use of TAS-114 and capecitabine may fulfill the need for more efficacious treatment for patients with advanced solid tumors.

The study, evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of the TAS-114/ capecitabine regimen in patients with advanced solid tumors, will be conducted in two parts: a Dose-Escalation Phase (Part 1) to determine the MTD; and an Expansion Phase (Part 2) to further evaluate the safety and preliminary efficacy with the MTD.

Inclusion Criteria:

1. Provided written consent

2. Is 18 years of age or older

3. Has histologically or cytologically confirmed advanced, measurable or non-measurable metastatic solid tumors for which the patients have no available therapy to convey clinical benefit Expansion Phase only: The target population should include at least

   1. 12 patients with breast cancer for whom 5 FU chemotherapy is the standard treatment
   2. 28 patients with refractory colorectal cancer.

4. May have received prior therapies for advanced or metastatic disease

5. Expansion Phase only: Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Version 1.1, 2009), ie, has at least one measurable lesion

6. Has ECOG performance status 0 or 1 on Cycle 1, Day 1

7. Is able to take medications orally

8. Has adequate organ function as defined by protocol

9. Women of childl-bearing potential must have a negative pregnancy test within 7 days prior to starting the study drug. Beth males and females must agree to adequate birth control if conception is possible during the study and for 6 months after the last dose

10. Is willing to and able to comply with scheduled visits and study procedures.

Exclusion Criteria:

1. Has a known DPD deficiency
2. Has had certain other recent treatment e.g. major surgery, anticancer therapy, extended field radiation, received investigational agent, within the specified time frames prior to study drug administration.
3. Certain serious illnesses or medical conditions
4. Is receiving concomitant treatment with drugs that may interact with capecitabine
5. Has had prior gastrectomy
6. Has known sensitivity to capecitabine or metabolites
7. Is a pregnant or lactating female