Global Safety T-DM1 Trial

Tahapan Penelitian : Initial
Mitra Pelaksana:
(1) Rumah Sakit Umum Pusat Nasional Dr. Cipto Mangunkusumo, (2) MRCCC Siloam Hospitals Semanggi, (3) Rumah Sakit Kanker Dharmais
No Registry
Tanggal Input Registry : 21-07-2016

The primary objective of this study is to evaluate the safety and tolerability of trastuzumab emtansine.
- The secondary objectives of this study are: - Progression-Free Survival (PFS) - Overall Survival (OS - Overall Response Rate (ORR) = partial response (PR) + complete response (CR) - Clinical Benefit Rate (CBR) - Duration of Response (DoR) - Time to Response (TTR) - The pharmacoeconomics outcome objective for this study is as follows: To evaluate the resource expenditures, while on study treatment, due to hospitalizations that are not study-defined evaluations. The number of hospital visits, number of days admitted, and type of visits (emergency department versus inpatient care) will be recorded
Global Safety T-DM1 Trial
A Two-Cohort, Open-Label, Multicenter, Study of Trastuzumab Emtansine (T-DM1) in HER2 Positive Locally Advanced or Metastatic Breast Cancer Patients Who Have Received Prior Anti-HER2 and Chemotherapy-Based Treatment
- Test product: Trastuzumab emtansine (T-DM1) - Target population: This study will enroll patients with human epidermal growth factor receptor 2 (HER2)positive, unresectable, locally advanced breast cancer (LABC) or metastatic breast cancer (mBC) who have previously received prior anti-HER2 and chemotherapy treatment and have progressed on or after the most recent treatment for LABC or mBC, or within 6 months of completing adjuvant therapy. - Study design: Patients will be divided into two cohorts: Cohort 1 (2000 patients) and Cohort 2 (220 patients only of Asian race). Patients in each cohort will receive trastuzumab emtansine until one of the following conditions, whichever occurs first: unacceptable toxicity, withdrawal of consent, disease progression, death, or up to a maximum of 2 years after the last patient has been enrolled into Cohort 1 (for patients in Cohort 1) or Cohort 2 (for patients in Cohort 2)

Inclusion Criteria:

Inclusion criteria: 1. HER2-positive disease determined locally i.e., IHC 3 + and/or gene-amplified by ISH as per institutional practice (however, both tests should be performed wherever possible and only one positive result is required for eligibility) 2. Histologically or cytologically confirmed invasive BC 3. Prior treatment for BC in the adjuvant, unresectable, locally advanced or metastatic setting must include both chemotherapy, alone or in combination with another agent, and an anti-HER2 agent, alone or in combination with another agent (complementary hormonal therapy is allowed) 4. Documented progression of incurable, unresectable, locally advanced, or mBC, defined by the investigator: progression must occur during or after most recent treatment for locally advanced/mBC or within 6 months of completing adjuvant therapy 5. Measurable and/or non-measurable disease 6. Signed written informed consent approved by the institution’s independent Ethics Committee (EC) 7. Age ≥ 18 years 8. LVEF ≥ 50% by either ECHO or MUGA 9. ECOG performance status of 0, 1 or 2 10. Adequate organ function: - Absolute neutrophil count > 1,500 cells/mm^3 - Platelet count > 100,000 cells/mm^3 - Hemoglobin > 9.0 g/dL. Patients are allowed to be transfused red blood cells to this level - Albumin ≥ 2.5 g/dL - Total bilirubin ≤ 1.5 × ULN) SGOT or AST, SGPT or ALT, and alkaline phosphatase ≤ 2.5 x ULN with the following exception: Patients with bone metastases: alkaline phosphatase ≤ 5 x ULN - Creatinine CL > 50 mL/min based on Cockroft-Gault glomerular filtration rate (GFR) estimation: (140 − Age) x (weight in kg) x (0.85 if female)/(72 x serum creatinine) - International normalized ratio (INR) (unless on therapeutic anti-coagulation) 11. For women of childbearing potential and men with partners of childbearing potential, agreement by the patient and/or partner to use a highly effective non-hormonal form of contraception such as surgical sterilization or two effective forms of non-hormonal contraception 12. Negative serum pregnancy test for women of childbearing potential (including pre-menopausal women who have had a tubal ligation) and for all women not meeting the definition of postmenopausal ( ≥ 12 months of amenorrhea), and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy. For all other women, documentation must be present in medical history confirming that the patient is not of childbearing potential. 13. For Cohort 2, only patients of Asian race will be enrolled

Exclusion Criteria:

Exclusion criteria: 1. History of treatment with trastuzumab emtansine 2. Prior enrollment into a clinical study containing trastuzumab emtansine regardless of having received trastuzumab emtansine or not 3. Peripheral neuropathy of Grade ≥ 3 per NCI CTCAE version 4.0 4. History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, synchronous or previously diagnosed HER2-positive BC 5. History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to first study treatment except hormone therapy, which can be given up to 7 days prior to first study treatment; recovery of treatment-related toxicity consistent with other eligibility criteria 6. History of exposure to the following cumulative doses of anthracyclines: - Doxorubicin or liposomal doxorubicin > 500 mg/m^2 - Epirubicin > 900 mg/m^2 - Mitoxantrone > 120 mg/m^2 - If another anthracycline, or more than one anthracycline, has been used, the cumulative dose must not exceed the equivalent of 500 mg/m^2 doxorubicin 7. History of radiation therapy within 14 days of first study treatment. The patient must have recovered from any resulting acute toxicity (to Grade ≤ 1) prior to first study treatment 8. Metastatic central nervous system (CNS) disease only 9. Brain metastases which are symptomatic. NOTE: a 14 day window after end of radiotherapy must be observed. Patient must not be receiving steroids to control symptoms 10. History of a decrease in LVEF to < 40% or symptomatic CHF with previous trastuzumab treatment 11. History of symptomatic CHF (New York Heart Association [NYHA] Classes II−IV) or serious cardiac arrhythmia requiring treatment 12. History of myocardial infarction or unstable angina within 6 months of first study treatment 13. Current dyspnea at rest due to complications of advanced malignancy or requirement for continuous oxygen therapy 14. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) 15. Pregnancy or lactation 16. Currently known active infection with HIV, hepatitis B virus, or hepatitis C virus 17. History of intolerance (such as Grade 3−4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins or any component of the product 18. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol throughout
(1) 773/UN2.F1/ETIK/2015, (2) 774/UN2.F1/ETIK/2015, (3) KEPK/033/VIII/2015
(1) Cosphiadi Irawan (, (2) Andhika Rachman (, (3) Nugroho Prayogo (