A Study in Patients With Hormone Receptor-Positive, Metastatic HER2-positive Breast Cancer.
- Conditions
- Health Condition 1: null- Breast Cancer
- Registration Number
- CTRI/2012/08/002900
- Lead Sponsor
- Roche Products India Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 250
1. Signed written informed consent approved by
the relevant IRB.
2. Age greater than or equal to 18 years.
3. Postmenopausal status >1 year (fulfilling one
or more of National Comprehensive Cancer
Network [NCCN] guideline criteria, version 2.
2011; Appendix 7).
4. Histologically or cytologically confirmed and
documented adenocarcinoma of the breast with
metastatic or locally advanced disease not
amenable to curative resection.
5. HER2-positive (defined as either IHC 3+ or
ISH positive) as assessed by local laboratory
on primary or metastatic tumor (ISH
positivity is defined as a ratio of 2.0 or
greater for the number of HER2 gene copies to
the number of signals for CEP17, or for
single probe tests, a HER2 gene count greater
than 4).
6. Hormone receptor-positive defined as estrogen
receptor (ER)-positive and/or progesterone
receptor (PgR)-positive assessed locally as
defined by institutional criteria.
7. At least one measurable lesion and/or non-
measurable disease evaluable according to
Response Evaluation Criteria In Solid Tumors
(RECIST) version 1.1 (Eisenhauer et al. 2009).
8. Eastern Cooperative Oncology Group (ECOG)
performance status 0 or 1.
9. LVEF of at least 50%.
10.Life expectancy of at least 12 weeks.
1. Previous systemic non-hormonal anticancer
therapy in the metastatic or locally advanced
breast cancer setting.
2. Disease-free interval from completion of
adjuvant or neo-adjuvant systemic non-
hormonal treatment to recurrence of within 6
months.
3. Previous approved or investigative anti-HER2
agents in any breast cancer treatment
setting, except trastuzumab and/or lapatinib
in the neoadjuvant or adjuvant setting.
4. Disease progression while receiving
trastuzumab and/or lapatinib in the adjuvant
setting.
5. History of persistent grade 2 or higher (NCI-
CTC, Version 4.0) hematological toxicity
resulting from previous adjuvant or neo-
adjuvant therapy.
6. Radiographic evidence of central nervous
system (CNS) metastases as assessed by CT or
MRI.
7. Current peripheral neuropathy of grade 3 or
higher (NCI-CTC, Version 4.0).
8. History of other malignancy within the last 5
years, except for carcinoma in situ of the
cervix or basal cell carcinoma.
9. Serious uncontrolled concomitant disease that
would contraindicate the use of any of the
investigational drugs used in this study or
that would put the patient at high risk for
treatment related complications.
10. Inadequate organ function, evidenced by the
following laboratory results:
a) Absolute neutrophil count 1,500 cells/mm3.
b) Platelet count 100,000 cells/mm3.
c) Hemoglobin 9 g/dL.
Total bilirubin greater than the upper limit
of normal (ULN) (unless the patient has
documented Gilbertâ??s syndrome).
AST (SGOT) or ALT (SGPT) 2.5 Ã? ULN.
AST (SGOT) or ALT (SGPT) 1.5 Ã? ULN with
concurrent serum alkaline phosphatase 2.5 Ã?
ULN Serum alkaline phosphatase may be 2.5 Ã?
ULN only if bone metastases are present and
AST (SGOT) and ALT (SGPT) 1.5 Ã? ULN.
Serum creatinine 2.0 mg/dL or 177 μmol/L.
International normalized ratio (INR) and
activated partial thromboplastin time (aPTT)
or partial thromboplastin time (PTT) 1.5 Ã?
ULN (unless on therapeutic coagulation).
11. Uncontrolled hypertension (systolic 150 mm
Hg and/or diastolic 100 mm Hg) or clinically
significant (i.e. active) cardiovascular
disease: cerebrovascular accident
(CVA)/stroke or myocardial infarction within
6 months prior to first study medication,
unstable angina, congestive heart failure
(CHF) of New York Heart Association (NYHA)
grade II or higher, or serious cardiac
arrhythmia requiring medication.
12. Current known infection with HIV, HBV, or
HCV.
13. Dyspnea at rest due to complications of
advanced malignancy, or other disease
requiring continuous oxygen therapy.
14. Major surgical procedure or significant
traumatic injury within 28 days prior to
randomization or anticipation of need for
major surgery during the course of study
treatment.
15. Lack of physical integrity of the upper
gast
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To compare progression-free survival (PFS) of pertuzumab given in combination with trastuzumab plus an aromatase inhibitor (AI) versus trastuzumab plus an AI. <br/ ><br> <br/ ><br>The primary efficacy endpoint is PFS. Analysis of PFS will be performed when 165 events have occurred.Timepoint: Tumor Evaluation: <br/ ><br>1] Every 3 cycles post <br/ ><br> Randomization. <br/ ><br>2] Safety Follow-up after <br/ ><br> end of treatment. <br/ ><br>3] 3 monthly post treatment <br/ ><br> follow-up after safety <br/ ><br> follow-up <br/ ><br>for points 2 and 3 Tumor evaluation to be done until disease progression not yest established.
- Secondary Outcome Measures
Name Time Method To compare pertuzumab given in combination with trastuzumab plus an AI versus trastuzumab plus an AI with respect to: <br/ ><br>Overall survival (OS) <br/ ><br>Overall response rate (ORR) <br/ ><br>Clinical benefit rate (CBR) <br/ ><br>Duration of response <br/ ><br>Time to response <br/ ><br>Safety and tolerability <br/ ><br>Quality of life (EQ-5D questionnaires) <br/ ><br>Timepoint: A first analysis of OS will be performed with the final analysis of PFS. The final analysis of OS will take place once all patients have been followed up for at least 24 months after the last patient is randomized, unless they have been lost to follow-up, withdrawn consent, or died, whichever occurs first. All other secondary endpoints will be summarized with the final analysis of PFS.