A randomized, 3 arm, multicentre, phase III study to evaluate the efficacy and the safety of T-DM1 combined with pertuzumab or T-DM1 combined with pertuzumab-placebo (blinded for pertuzumab), versus the combination of trastuzumab plus taxane, as first line treatment in HER2- positive progressive or recurrent locally advanced or metastatic breast cancer (MBC). - MARIANNE
- Conditions
- First line treatment in HER2 positive progressive or recurrent locally advanced or metastatic breast cancer (MBC)MedDRA version: 18.0Level: 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]MedDRA version: 18.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.0Level: PTClassification code 10006198Term: Breast cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2009-017905-13-HU
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1095
a) Disease specific inclusion criteria:
1. HER2-positive breast cancer as defined by IHC 3+ and /or ISH positive, prospectively confirmed by a Sponsor designated central laboratory prior to enrollment. Archival tumor samples obtained from primary or metastatic sites are acceptable.
2. Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and be a candidate for chemotherapy. Patients with locally advanced disease must have recurrent or progressive disease, which must not be amenable to resection with curative intent. Patients with standard curative options available to them are not eligible.
3. Patients must have measurable and/or non-measurable disease which must be evaluable per RECIST 1.1.
b) General inclusion criteria:
4. Signed written informed consent approved by the institution’s Independent Ethical Committee (IEC).
5. Age = 18 years.
6. ECOG Performance Status 0 or 1.
7. Adequate organ function as determined by the following laboratory results, within approximately 14 days prior to randomization:
8. For women of childbearing potential and men with partners of childbearing potential, agreement to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner and to continue its use for the duration of study treatment and for 6 months after the last dose of study treatment. Male patients whose partners are pregnant must use condoms for the duration of the study treatment and for 6 months after the last dose of study treatment. Specific country and/or local requirements for contraception will be followed.
9. A negative serum pregnancy test must be available for premenopausal women and for women less than 12 months after the onset of menopause.
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 874
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 218
a) Disease related Exclusion Criteria:
1. History of systemic anti-cancer therapy after the diagnosis of MBC cancer or for recurrent locally advanced disease with the
exception of prior hormonal regimens for recurrent locally
advanced disease or MBC.
2. An interval of < 6 months from the last dose of vincaalkaloid or taxane cytotoxic chemotherapy in the neoadjuvant or adjuvant setting until the time of metastatic
diagnosis.
3. Hormone therapy < 7 days prior to randomization.
4. Trastuzumab and/or lapatinib (neoadjuvant/adjuvant setting) < 21 days prior to randomization.
5. Prior trastuzumab emtansine or pertuzumab therapy.
6. Treatment with any anti-cancer investigational drug within 28 days prior to commencing study treatment.
7. History of other malignancy within the last 5 years except for appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, Stage I uterine cancer, or other malignancies with an expected curative outcome.
8. Brain metastases (symptomatic or not symptomatic) that have not been treated previously, are progressive or require any type of therapy (e.g., radiation, surgery, or steroids) to control symptoms from brain metastases within 60 days prior to the first study treatment dose.
9. Radiotherapy for metastatic sites of disease outside of the
brain performed within 14 days prior to study enrollment
and/or radiation of > 30% of marrow-bearing bone.
10. Symptomatic hypercalcemia requiring use of bisphosphonate therapy within 21 days prior to the first study treatment. Patients who receive bisphosphonate therapy specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible.
11. Current peripheral neuropathy Grade = 2 per NCI-CTCAE version 4.0.
12. Abnormal liver function
13. History of exposure to the following cumulative doses of anthracyclines as specified below.
o Doxorubicin > 500 mg/m2
o Liposomal doxorubicin > 500 mg/m2
o Epirubucin > 720 mg/m2
o Mitoxantrone > 120 mg/m2
o Idarubicin > 90 mg/m2
If another anthracycline or more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin.
14. Cardiopulmonary dysfunction b) General exclusion criteria:
15. Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary or metabolic disease; wound healing disorders; ulcers; bone fractures).
16. Current pregnancy and lactation.
17. Major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment.
18. Concurrent, serious, uncontrolled infections or current known infection with HIV or active hepatitis B and/or hepatitis C.
19. Current chronic daily treatment with corticosteroids (dose of > 10 mg/day methylprednisone equivalent).
20. History of intolerance, including Grade 3-4 infusion reaction or hypersensitivity to trastuzumab, murine proteins or docetaxel/paclitaxel.
21. Known hypersensitivity to any of the study drugs, including excipients, of any drugs formulated in polysorbate 80.
22. Assessment by the investigator to be unable or unwilling to comply with the requirements of the protocol.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method