Efficacy and Safety of Everolimus in Combination Therapy, in Patients With HER2-overexpressing Metastatic Breast Cancer
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT00426556
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 88
- 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
- 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
Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase I - RAD001 5mg + PT, daily Everolimus Daily dosing schedule of EPT = Paclitaxel \& Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab. Phase I - RAD001 5mg + PT, daily Trastuzumab Daily dosing schedule of EPT = Paclitaxel \& Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab. Phase I - RAD001 10mg + PT, daily Everolimus Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab Phase I - RAD001 10mg + PT, daily Paclitaxel Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab Phase I - RAD001 5mg + PT, daily Paclitaxel Daily dosing schedule of EPT = Paclitaxel \& Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab. Phase I - RAD001 10mg + PT, daily Trastuzumab Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab Phase I - RAD001 30mg + PT, weekly Trastuzumab Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab. Phase I - RAD001 30mg + PT, weekly Everolimus Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab. Phase I - RAD001 30mg + PT, weekly Paclitaxel Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab. Phase II - RAD001 10mg + PT, daily Everolimus Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab Phase II - RAD001 10mg + PT, daily Paclitaxel Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab Phase II - RAD001 10mg + PT, daily Trastuzumab Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
- Primary Outcome Measures
Name Time Method Phase II: Overall Response Rate every 8 - 9 weeks until disease progression or a new lesion is identified 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.
- Secondary Outcome Measures
Name Time Method Phase I: Best Overall Response (BOR) every 8 - 9 weeks until disease progression or a new lesion is identified BOR was determined based on investigator assessment of overall lesion response using RECIST criteria guidelines. BOR = objective responses rate (ORR), disease control rate (DCR) or clinical benefit rate (CBR). ORR = (complete response (CR) or partial response(PR); DCR = (CR or PR or Stable disease (SD); CBR = (CR or PR or SD \>= 24 weeks).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; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for partial disease (PD). PD = At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.
Phase II: Progression Free Survival (PFS) every 8 - 9 weeks until disease progression or a new lesion is identified PFS is defined as the time from start of treatment to the date of first documented progression or death due to any cause. If a patient has not had an event, PFS will be censored at the date of last adequate tumor assessment.
Phase II: Overall Survival (OS) every 3 months until death Overall survival (OS) is defined as the time from start of treatment to the date of death due to any cause. If a patient is not known to have died, survival was censored at the last date of contact. OS was to be reported at extension and after 3-year follow-up. The Kaplan-Meier median was used to analyze the OS.
Trial Locations
- Locations (12)
Compassionate Cancer Care Medical Group Dept.ofCCCMG
🇺🇸Fountain Valley, California, United States
University of California at Los Angeles Dept.of UCLA Dept.ofMed.
🇺🇸Los Angeles, California, United States
Cancer Centers of the Carolinas CC of C -Eastside
🇺🇸Greenville, South Carolina, United States
Novartis Investigative Site
🇪🇸Lleida, Cataluna, Spain
Loma Linda University Dept.ofLomaLindaCancerCent(3)
🇺🇸Loma Linda, California, United States
Sammons Cancer Center - Texas Oncology
🇺🇸Dallas, Texas, United States
Emory University School of Medicine/Winship Cancer Institute Dept. of Hematology (2)
🇺🇸Atlanta, Georgia, United States
North Shore University Health System
🇺🇸Evanston, Illinois, United States
Wilshire Oncology Medical Group La Verne
🇺🇸*see Various Departments*, California, United States
Florida Cancer Research Institute
🇺🇸Davie, Florida, United States
Peninsula Regional Medical Center Deptof Oncology and Hematology
🇺🇸Salisbury, Maryland, United States
Washington University School Of Medicine-Siteman Cancer Ctr StudyCoordinator:CRAD001J2101
🇺🇸St. Louis, Missouri, United States