Efficacy and Safety of Everolimus in Combination Therapy, in Patients With HER2-overexpressing Metastatic Breast Cancer
A Phase Ib/II Study Investigating the Combination of Everolimus With Trastuzumab and Paclitaxel in Patients With HER2-overexpressing Metastatic Breast Cancer
2 other identifiers
interventional
88
5 countries
20
Brief Summary
Phase I: will look at different dose levels and regimens of everolimus combined with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast cancer. Phase II: will assess the efficacy and safety of the 10mg daily dose of everolimus combined with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2007
Longer than P75 for phase_1
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 23, 2007
CompletedFirst Posted
Study publicly available on registry
January 24, 2007
CompletedStudy Start
First participant enrolled
July 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2014
CompletedResults Posted
Study results publicly available
March 31, 2015
CompletedDecember 28, 2015
November 1, 2015
6.7 years
January 23, 2007
March 20, 2015
November 24, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Phase II: Overall Response Rate
The primary objective of this phase II study was to evaluate the efficacy of the dose level/regimen of everolimus recommended from the Phase I with trastuzumab and paclitaxel (PT) therapy in patients with HER2-overexpressing metastatic breast cancer whose disease progressed on/after trastuzumab mono-and/or combination therapy based on the evaluation of objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Objective response rate (ORR) was defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR). Only patients with measurable disease (the presence of at least one measurable lesion) at baseline were included in the study. CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.
every 8 - 9 weeks until disease progression or a new lesion is identified
Secondary Outcomes (3)
Phase I: Best Overall Response (BOR)
every 8 - 9 weeks until disease progression or a new lesion is identified
Phase II: Progression Free Survival (PFS)
every 8 - 9 weeks until disease progression or a new lesion is identified
Phase II: Overall Survival (OS)
every 3 months until death
Study Arms (4)
Phase I - RAD001 5mg + PT, daily
EXPERIMENTALDaily dosing schedule of EPT = Paclitaxel \& Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab.
Phase I - RAD001 10mg + PT, daily
EXPERIMENTALDaily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
Phase I - RAD001 30mg + PT, weekly
EXPERIMENTALWeekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab.
Phase II - RAD001 10mg + PT, daily
EXPERIMENTALDaily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
Interventions
Everolimus (RAD001) was supplied as tablets in 3 different dosage strengths, 2.5, 5, and 10 mg. The drug was packaged in blisters containing 10 tablets per blister. Blisters and packaging labels were compliant with local regulations and were printed in local language.
Commercially-available trastuzumab was used in this study. A 4 mg/kg loading dose was administered, intra-venous (IV), over 90 minutes on Day 1 (if patient was not already receiving trastuzumab); this was followed by weekly trastuzumab 2 mg/kg IV administered over 30 minutes. For patients who continued to receive trastuzumab and everolimus after completion/discontinuation of chemotherapy in the core treatment phase, trastuzumab may have been administered once every 3 weeks at a dose of 6 mg/kg. PT = Paclitaxel \& Trastuzumab
Commercially-available paclitaxel was used in this study. Paclitaxel infusion was administered on Days 1, 8, and 15 of each 28-day cycle, after administration of trastuzumab. Paclitaxel (80 mg/m2) was administered as a 60-minute continuous IV infusion after standard premedication. Patients received paclitaxel for 6 cycles. At the investigator's discretion, treatment with paclitaxel could continue beyond 6 cycles.
Eligibility Criteria
You may qualify if:
- Female or male patients ≥ 18 years old with WHO performance status ≤ 1
- HER-2 over-expressing metastatic breast cancer cells confirmed by histology
- Progressive disease on prior trastuzumab alone/or in combination with other anticancer agents, or relapsed any time after completion of this therapy (phase l)
- Patient resistance to trastuzumab and taxanes (Phase ll)
- Measurable disease according to RECIST (Phase ll)
- Patients neurologically stable with adequate bone marrow, liver and renal function
You may not qualify if:
- Patients receiving endocrine therapy for breast cancer ≤ 2 weeks prior to study treatment start
- Patients currently receiving chemotherapy, immunotherapy or radiotherapy or who have received these ≤ 4 weeks prior to study treatment start or patients who have received lapatinib ≤ 2 weeks prior to study treatment start
- Patients who have previously received mTOR inhibitors
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (20)
Wilshire Oncology Medical Group La Verne
*see Various Departments*, California, United States
Compassionate Cancer Care Medical Group Dept.ofCCCMG
Fountain Valley, California, 92708, United States
Loma Linda University Dept.ofLomaLindaCancerCent(3)
Loma Linda, California, 92354, United States
University of California at Los Angeles Dept.of UCLA Dept.ofMed.
Los Angeles, California, 90095, United States
Florida Cancer Research Institute
Davie, Florida, 33328, United States
Emory University School of Medicine/Winship Cancer Institute Dept. of Hematology (2)
Atlanta, Georgia, 30322, United States
North Shore University Health System
Evanston, Illinois, 60201, United States
Peninsula Regional Medical Center Deptof Oncology and Hematology
Salisbury, Maryland, 21801, United States
Washington University School Of Medicine-Siteman Cancer Ctr StudyCoordinator:CRAD001J2101
St Louis, Missouri, 63110, United States
Cancer Centers of the Carolinas CC of C -Eastside
Greenville, South Carolina, 29605, United States
Sammons Cancer Center - Texas Oncology
Dallas, Texas, 78246, United States
Novartis Investigative Site
Charleroi, 6000, Belgium
Novartis Investigative Site
Liège, 4000, Belgium
Novartis Investigative Site
Turnhout, 2300, Belgium
Novartis Investigative Site
Paris, 75970, France
Novartis Investigative Site
Saint-Herblain Cédex, 44805, France
Novartis Investigative Site
Toulouse, 31059, France
Novartis Investigative Site
Villejuif, 94805, France
Novartis Investigative Site
Maastricht, 6229 HX, Netherlands
Novartis Investigative Site
Lleida, Catalonia, 25198, Spain
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 23, 2007
First Posted
January 24, 2007
Study Start
July 1, 2007
Primary Completion
March 1, 2014
Study Completion
March 1, 2014
Last Updated
December 28, 2015
Results First Posted
March 31, 2015
Record last verified: 2015-11