A study in patients with HER2-positive breast cancer that has spread and has not responded to one course of anti-cancer therapy.
- Conditions
- HER2 positive metastatic breast cancerMedDRA version: 20.0Level: PTClassification code 10065430Term: HER-2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-001628-37-EE
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 2003
1. HER2-positive disease determined locally i.e., IHC 3 + and/or gene-amplified by in-situ hybridization (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 advanced/metastatic, unresectable locally advanced or metastatic setting must include an anti-HER2 agent and chemotherapy in combination or sequential administration (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 after 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. Left ventricular ejection fraction = 50% by either ECHO or MUGA
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
10. Adequate organ function
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.
12. Negative serum pregnancy test for women of childbearing potential and for all women not meeting the definition of postmenopausal, 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
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 1909
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 311
1. History of treatment with trastuzumab emtansine
2. Prior enrolment 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 breast cancer
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/m2
• Epirubicin > 900 mg/m2
• Mitoxantrone >120 mg/m2
• If another anthracycline, or more than one anthracycline, has been used, the cumulative dose must not exceed the equivalent of 500 mg/m2 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. Metstatic CNS disease only
9. Brain metastases which are symptomatic. NOTE: A 14 days 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 congestive heart failure (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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to evaluate the safety and tolerability of trastuzumab emtansine. ;Secondary Objective: •Progression free survival (PFS)<br>•Overall survival (OS)<br>•Overall response rate (ORR) = partial response (PR) + complete response (CR)<br>•Clinical benefit rate (CBR)<br>•Duration of response (DoR)<br>•Time To Response (TTR)<br>Pharmacoeconomics outcome objective<br>•Health Resource Utilization;Primary end point(s): The primary endpoint in this study will be AEs Grade 3 or higher for hepatic events, allergic reactions, thrombocytopenia, hemorrhage events, also all other AEs Grade 3 or higher related to trastuzumab emtansine, and pneumonitis of all grades. ;Timepoint(s) of evaluation of this end point: The final analysis will be performed when all patients have been followed up for safety and efficacy for a period of up to 2 years after the last patient has been enrolled in Cohort 2 of the trial.<br>
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Efficacy is the secondary endpoint. Efficacy endpoints will be: PFS, OS, ORR, CBR, duration of response, and time to tumor response.<br>;Timepoint(s) of evaluation of this end point: The final analysis will be performed when all patients have been followed up for safety and efficacy for a period of up to 2 years after the last patient has been enrolled in Cohort 2 of the trial.<br>