- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00674414
Trastuzumab With or Without Everolimus in Treating Women With Breast Cancer That Can Be Removed By Surgery
A Phase II, Randomized, Multi-center Study, Assessing Value of Adding Everolimus (RAD001) to Trastuzumab as Preoperative Therapy of HER-2 Positive Primary Breast Cancer Amenable to Surgery.
RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with trastuzumab is more effective than giving trastuzumab alone in treating women with breast cancer.
PURPOSE: This randomized phase II trial is studying trastuzumab and everolimus to see how well they work compared to trastuzumab alone before surgery in treating patients with breast cancer that can be removed by surgery.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
OBJECTIVES:
Primary
- To evaluate the added efficacy obtained by the association of trastuzumab (Herceptin®) with everolimus as preoperative therapy of primary HER2-positive breast cancer as shown by increased clinical tumor response rate.
Secondary
- To compare the inhibition of the two pathways, RAS/RAF/MAP kinase and PI3-kinase/AKT/mTor.
- To evaluate whether the pre-treatment molecular characteristics of tumor and serum or their modifications early in the treatment are predictive of clinical response.
- To compare the frequency of pathological complete response achieved in the two groups after 6 weeks of treatment.
- To determine disease-free survival at 3 years.
- To evaluate safety and tolerability of the two treatment regimens.
- To analyze the possible relationships between treatment toxicity and constitutional gene polymorphisms linked to the administered agents.
- To analyze the possible relationships between response and molecular pharmacodynamic assessments, including proteomics (blood samples), Bio-Plex protein array (tumor), and IHC (tumor).
- To analyze the drug levels and pharmacokinetic assessments of everolimus and trastuzumab (Herceptin®).
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive trastuzumab (Herceptin®) IV once weekly for 6 weeks. Patients then undergo surgery.
- Arm II: Patients receive trastuzumab as in arm I and oral everolimus once daily for 6 weeks. Within 24 hours after completing everolimus, patients undergo surgery.
Blood and tumor samples are collected periodically during study for pharmacogenomic, proteomic, and pharmacokinetic studies.
After completion of study treatment, patients are followed periodically for up to 3 years.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Lille, France, 59020
- Centre Oscar Lambret
-
Lyon, France, 69373
- Centre Léon Berard
-
Marseille, France, 13273
- Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
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Nantes-Saint Herblain, France, 44805
- Centre Regional Rene Gauducheau
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Nice, France, 06189
- Centre Antoine Lacassagne
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Paris, France, 75248
- Institut Curie Hopital
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Vandoeuvre-les-Nancy, France, 54511
- Centre Alexis Vautrin
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Villejuif, France, F-94805
- Institut Gustave Roussy
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Histologically confirmed diagnosis of invasive breast cancer
- Previously untreated disease
Candidate for breast-conserving surgery, as defined by both of the following:
- Clinical stage cT1-3, cN0-2 disease
- Clinical stage M0 disease (bone scan, chest X-ray, and liver ultrasound required at screening to exclude metastatic disease)
HER2-positive primary tumor, defined as meeting either of the following criteria:
- IHC 3+
- IHC 2+ and FISH positive (centralized confirmation)
No inflammatory breast cancer or bilateral breast cancer
- Patients who have been treated for cancer of the contralateral breast can be included if there is at least a 5 year time interval from last systemic treatment for breast cancer before randomization into this study
- Hormone receptor status not specified
PATIENT CHARACTERISTICS:
- WHO performance status 0-1
- Menopausal status not specified
- WBC ≥ 3.5 x 10^9/L
- ANC ≥ 1.5 x 10^9/L
- Platelet count ≥ 100 x 10^9/L
- Hb ≥ 10 g/dL
- Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Serum transaminases activity ≤ 2.5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
- Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
- FEV > 55% by MUGA or ECHO
- Spirometry and DLCO > 50% of normal
- O_2 saturation > 88% at rest on room air
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No known hypersensitivity to everolimus, sirolimus, trastuzumab (Herceptin®), or lactulose
No hypercholesterolemia/hypertriglyceridemia ≥ grade 3
- No hypercholesterolemia/hypertriglyceridemia ≥ grade 2 with history of coronary artery disease (despite lipid-lowering treatment if given)
- No uncontrolled infection
No other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including any of the following:
- Uncontrolled hypertension
- Congestive cardiac failure
- Ventricular arrhythmias
- Active ischemic heart disease
- Myocardial infarction within the past year
- Chronic liver or renal disease
- Active gastrointestinal tract ulceration
- Severely impaired lung function
- No known history of HIV seropositivity
- No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Willing to participate in the biological investigations
- Not deprived of liberty or placed under guardianship
- Patients must be affiliated to a Social Security System
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 30 days (from the screening visit) since prior other investigational drugs
More than 5 days (from randomization) since prior and no concurrent strong inhibitors or inducers of the isoenzyme CYP3A, including any of the following
- Rifabutin
- Rifampicin
- Clarithromycin
- Ketoconazole
- Itraconazole
- Voriconazole
- Ritonavir
- Telithromycin
- No other concurrent anti-cancer treatments such as chemotherapy, immunotherapy/biological response modifiers, endocrine therapy, or radiotherapy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Arm I
Patients receive trastuzumab (Herceptin®) IV once weekly for 6 weeks.
Patients then undergo surgery.
|
Patients undergo surgery
Trastuzumab (Herceptin®) IV once weekly
|
Experimental: Arm II
Patients receive trastuzumab as in arm I and oral everolimus once daily for 6 weeks.
Within 24 hours after completing everolimus, patients undergo surgery.
|
Patients undergo surgery
Trastuzumab (Herceptin®) IV once weekly
Oral everolimus once daily
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Efficacy as measured by clinical and echographic tumor evaluation
Time Frame: january 2013
|
january 2013
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Disease-free survival at 3 years
Time Frame: January 2015
|
January 2015
|
Pathological response assessed after 6 weeks of treatment
Time Frame: January 2013
|
January 2013
|
Clinical response predictive factors
Time Frame: May 2013
|
May 2013
|
Rate of pathological complete response (pCR)
Time Frame: January 2013
|
January 2013
|
Pharmacogenomics, proteomics, immunohistochemistry (IHC), pharmacokinetics
Time Frame: december 2013
|
december 2013
|
Toxicity as assessed by the standard NCI CTC-AE v3.0 scale
Time Frame: January 2013
|
January 2013
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mario Campone, MD, Centre Regional Rene Gauducheau
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CDR0000595159
- FRE-FNCLCC-GEP-04/0606-RAD-HER
- EUDRACT-2007-004098-24
- EU-20851
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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