Patients with HER2-positive metastatic breast cancer that has progressed on trastuzumab
Conditions
Interventions
Cohort A T-DM1:day1(d.i.v) S-1:day1-day15(p.o.) Administrated every 3weeks Starting dose is level 0 Level 0 T-DM1:3.6mg/kg S-1:65mg/m2/day Level 1 T-DM1:3.6mg/kg S-1:80mg/m2/day CohortB
Sponsors
St Marianna University School of Medicine
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Histopathologically proven diagnosis of breast cancer. 2. Unresectable or metastatic breast cancer 3. Age at consent is >= 20 4. ECOG PS 0-2 5. One or more measurable lesion 6. HER2 positive tumor, defined as either IHC3+ alone or IHC 2+ in combination with FISH+. 7. Patients who received at least single administration of trastuzumab for neo-adjuvant, adjuvant or chemotherapy for metastatic breast cancer (History of administration of T-DM1 is also eligible). 8. Vital organ functions (listed below) are preserved within 14 days prior to entry. Neu. >= 1,500/cubicmillimeter Hb. >= 9.0 g/dL Plt. >= 100,000/cubicmillimeter T-bil. <= 1.5 mg/dL AST(GOT) <= 100 IU/L (<= 150 IU/L in case of liver metastasis) ALT(GPT) <= 100 IU/L (<= 150 IU/L in case of liver metastasis) Serum albumin >=2.5g/dL Serum creatinine <=1.5mg/dL Creatinine clearance >=50mL/minutes 9. Patients who is not received RBC transfusion before 14 days prior to entry 10. Women of childbearing potential (underwent menstruation within 1 year prior entry) should take a pregnancy test and give proof negative 14 days prior entry. 11. Residual <= Grade 1 per CTCAE v4.0 toxicity resulting previous therapy (e.g. chemotherapy, radiation, surgery). Alopecia, peripheral neuropathy, skin hyperpigmentation, dysgeusia is permitted. 12. Ability of oral administration. 13. Signed informed consent document
Exclusion criteria
Exclusion criteria: 1. Prior treatment with chemotherapy (including trastuzumab, T-DM1), hormone therapy, immune therapy or biologics with in 14 days prior to entry. 2. Invasive surgery within 28 days prior to enrollment. 3. Documented history of congestive heart failure of any New York Herat Association (NYHA) class II-IV, or >= grade 3 heart failure per CTCAE v4.0 4. Diagnosis as angina pectoris requiring treatment within 6 months prior entry. 5. Uncontrollable hypertension (not controlled by medication systolic blood pressure <150 mmHg and diastolic blood pressure <100 mmHg) 6. Baseline LVEF <50% 7. History of exposure to cumulative doses of anthracyclines (e.g. Doxorubicin>500mg/m2, Epirubicin>720 mg/m2). 8. History of >=Grade3 infusion reaction caused by Trastuzmab or T-DM1. 9. History of discontinue trastuzumab or T-DM1 reason for adverse event. 10. Not tolerable to S-1 or Capecitabine in prior therapy 11. History of intolerance to Trastuzumab added substance (e.g. sodium succinate, sucrose, polusorbate). 12. Patients who needs continuous administration of flucytosine, phenytoin, or warfarin potassium. 13. Patients have symptomatic or periodical medication for brain metastasis 14. >=grade 2 peripheral neuropathy. 15. Hyper sensitivity to fuluoropyrimidine or known dihydropyrimidine dehydrogenase (DPD) deficiency. 16. Current known viral hepatitis. 17. Active carcinoma affect to prognosis. 18. Congenial hemorrhage or clotting abnormality 19. Current serious, uncontrolled infection or current known HIV infection. 20. Any patient unwilling or unable to use adequate contraceptive measures during study treatment and for 7 months after the last dose of study treatment. 21. Any other condition, which in the opinion of the investigator or sub-investigator would preclude participation in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of dose limiting toxicity in each dose level at completion of first cycle | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of adverse events Response rate (RR) | — |
Countries
Japan
Contacts
Public ContactYasuyuki Kojima
St Marianna University School of Medicine Division of Breast and Endocrine Surgery, Department of Surgery
Outcome results
None listed