Treatment in patients with advanced, HER2-positive breast cancer MedDRA version: 14.1 Level: LLT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 100000004864 MedDRA version: 14.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: trastuzumab emtansine (T-DM1)
Product Code: RO5304020/F02-01
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent. 2. Age = 18 years. 3. ECOG PS of 0 or 1. 4. Life expectancy of = 12 weeks. 5. Histologically or cytologically confirmed breast cancer, which is documented to be metastatic or inoperable, locally advanced without meeting the LABC criteria, and amenable for treatment with docetaxel. 6. Evaluable (Feasibility Part only) or measurable (Extension Part) disease (as defined by RECIST 1.0). 7. HER2-positive disease locally confirmed by HER2 protein over expression. 8. History of progression within 3 months prior to study entry. for LABC Patients 9. Histologically or cytologically confirmed newly diagnosed locally advanced breast cancer defined as stage IIIa to stage IIIC disease according to the American Joint Committee on Cancer (AJCC) staging system [62]: • T2 to T4d tumor • Any N • M0 10. HER2-positive breast cancer as defined by IHC 3+ and/or FISH positive, prospectively confirmed by a Sponsor designated central laboratory prior to enrollment 11. Locally advanced breast cancer amenable for treatment with neoadjuvant docetaxel based chemotherapy 12. Patient agreement to undergo mastectomy or lumpectomy after neoadjuvant treatment Amenable to investigational therapy with the combination of T-DM1 and docetaxel prior to the initiation of standard of care. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 81 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating females. 2. Women of childbearing potential unless surgically sterile or using adequate measures of contraception (intra-uterine device or barrier method of contraception in conjunction with spermicidal jelly). 3. Patients must not have received radiotherapy for the treatment of metastatic or locally recurrent/advanced disease other than for the relief of the pain in progressing metastatic bone lesions (limited to < 30% of marrow bearing bone) and/or brain metastasis. Patients must have recovered from their radiotherapy-related toxicities. 4. Significant cardiac disease including but not confined to: - Inadequate left ventricular ejection function (LVEF) at baseline, as defined as LVEF =50% by either echocardiogram or MUGA. - New York Health Association (NYHA) Class =I congestive heart failure. - Current unstable angina or serious cardiac arrhythmia despite adequate medication. - Myocardial infarction or clinically significant valvular heart disease within the last 6 months prior to enrollment in the study. - History of exposure to high doses of anthracyclines. 5. Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability, which could affect ability to give informed consent, or compliance with study drugs. 6. Brain metastases that are untreated, symptomatic or require therapy to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastasis within 2 months of the first study treatment. CT or MRI scan of the brain is mandatory within 28 days of first treatment. 7. Treatment with any investigational drug within 30 days prior to commencing treatment with study drug. 8. Inadequate organ function of the a) Liver b) Kidney c) Bone marrow d) Peripheral nervous system:Peripheral neuropathy of =Grade 2 per NCI CTC for AE Version 3.0. 9. Patients with serious, uncontrolled, intercurrent illness including infections (bacterial or viral) and poorly controlled diabetes mellitus. 10. Patients with severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen. 11. Incomplete wound healing following major surgical procedure, open biopsy or significant traumatic injury or anticipation of the need for major surgery during the course of the study treatment. 10. Evidence of any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, or that may affect patient compliance with study routines, or places the patient at high risk from treatment related complications. 11. Known hypersensitivity to any of the study drugs, trastuzumab, murine proteins or excipients. 12. Inability to comply with the protocol. 13. Patients unable or unwilling to participate in the study. for MBC Patients: 14. Patients must not have received radiotherapy for the treatment of metastatic or locally recurrent/advanced disease other than for the relief of the pain in progressing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. every 3 weeks throughout treatment phase 2. every 3 weeks throughout the study and in follow-up phase at day 28, months 3 and 3monthly thereafter ; Primary end point(s): 1. safety and tolerability of increased docetaxel in combination with T-DM1, assessed by adverse events or dose limiting toxicity\n 2. safety and tolerability, dose limiting toxicity ;Main Objective: Feasibility Part: To evaluate the safety and tolerability profile of the combination docetaxel with T-DM1in patients with HER2+, inoperable, locally advanced or mBC. To evaluate the safety and tolerability of the combination of docetaxel and T-DM1 in patients with newly diagnosed HER2+ LABC and thereafter the safety and tolerability of the addition of pertuzumab to the combination trastuzumab emtansine with docetaxel. The dose of trastuzumab emtansine and docetaxel found to be feasible in MBC feasibility will be the starting dose for the LABC feasibility. Extension Part: In 2nd and 1st line MBC patients: To validate the safety and efficacy of the recommended T-DM1 dose in combination with docetaxel q3w as determined in the MBC feasibility part. In newly diagnosed LABC patients: To validate the safety and efficacy of the recommended TDM1 dose in combination with docetaxel and in combination with docetaxel and pertuzumab q3w, as determined in the LABC Feasibility Part of the study.; Secondary Objective: To evaluate the: • Toxicity profile of study drugs • Progression Free Survival (PFS). • Overall Response Rate (ORR). • Clinical Benefit Rate (CR, PR or SD for at least 6 months). • Duration of Response (DR). • Time to treatment failure (TTF). • Pharmacokinetic (PK) characteristics of T-DM1 when combined with docetaxel. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression Free Survival (PFS) 2. response rate and clinical benefit rate according to tumor assessment 3. toxicity profile ; Timepoint(s) of evaluation of this end point: 1. after cycles 2,4,6 and 8, and 12weekly thereafter 2. after cycles 2,4,6 and 8, and 12weekly thereafter throughout treatment phase 3. throughout the combination treatment period of the study, every 3 weeks | — |
Countries
France, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed