UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A Phase Ib study of Trastuzumab emtansine plus S-1 or Capecitabine in patients with previously trastuzumab treated metastatic breast cancer
Title of the study (Brief title)	A Phase Ib study of Trastuzumab emtansine plus S-1 or Capecitabine in patients with previously trastuzumab treated metastatic breast cancer(MARIA15-01)
Region	Japan

Condition
Condition	Patients with HER2-positive metastatic breast cancer that has progressed on trastuzumab
Classification by specialty	Breast surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To evaluate tolerability and safety of trastuzumab emtansine plus S-1 or Capecitabine in patients with previously trastuzumab treated metastatic breast cancer
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase I

Assessment
Primary outcomes	Proportion of dose limiting toxicity in each dose level at completion of first cycle
Key secondary outcomes	Incidence of adverse events Response rate (RR)

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	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 T-DM1:day1(d.i.v) Capesitabine:day1-day15(p.o.) Administrated every 3weeks Starting dose is level 0 Level 0 T-DM1:3.6mg/kg Capesitabine:1300mg/m2/day Level 1 T-DM1:3.6mg/kg Capesitabine:1400mg/m2/day
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Female
Key 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
Key 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
Target sample size	20

Research contact person
Name of lead principal investigator	Koichiro Tsugawa
Organization	St Marianna University School of Medicine
Division name	Division of Breast and Endocrine Surgery, Department of Surgery
Address	2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, Japan
TEL	044-977-8111
Email	koitsuga@marianna-u.ac.jp

Public contact
Name of contact person	Yasuyuki Kojima
Organization	St Marianna University School of Medicine
Division name	Division of Breast and Endocrine Surgery, Department of Surgery
Address	2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, Japan
TEL	044-977-8111
Homepage URL
Email	kojiyasu@marianna-u.ac.jp

Sponsor
Institute	St Marianna University School of Medicine
Institute
Department

Funding Source
Organization	CHUGAI PHARMACEUTICAL CO., LTD
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2015 Year 07 Month 23 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2015 Year 09 Month 01 Day
Anticipated trial start date	2015 Year 10 Month 29 Day
Last follow-up date	2017 Year 09 Month 30 Day
Date of closure to data entry	2017 Year 10 Month 31 Day
Date trial data considered complete	2017 Year 11 Month 30 Day
Date analysis concluded	2018 Year 01 Month 12 Day

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2015 Year 07 Month 22 Day
Last modified on	2018 Year 01 Month 23 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021216