Efficacy and Safety of Everolimus in Combination Therapy, in Patients With HER2-overexpressing Metastatic Breast Cancer

NCT ID: NCT00426556

Last Updated: 2015-12-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2014-03-31

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.

Conditions

Metastatic Breast Cancer

Keywords

Breast cancer; Cancer of the breast; Human mammary carcinoma; HER-2; Metastatic; everolimus; trastuzumab; paclitaxel

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I - RAD001 5mg + PT, daily

Daily dosing schedule of EPT = Paclitaxel \& Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab.

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

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.

Trastuzumab

Intervention Type: DRUG

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

Paclitaxel

Intervention Type: DRUG

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.

Phase I - RAD001 10mg + PT, daily

Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

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.

Trastuzumab

Intervention Type: DRUG

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

Paclitaxel

Intervention Type: DRUG

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.

Phase I - RAD001 30mg + PT, weekly

Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab.

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

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.

Trastuzumab

Intervention Type: DRUG

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

Paclitaxel

Intervention Type: DRUG

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.

Phase II - RAD001 10mg + PT, daily

Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

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.

Trastuzumab

Intervention Type: DRUG

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

Paclitaxel

Intervention Type: DRUG

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.

Interventions

Everolimus

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.

Intervention Type: DRUG

Trastuzumab

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

Intervention Type: DRUG

Paclitaxel

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.

Intervention Type: DRUG

Other Intervention Names

RAD001

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Wilshire Oncology Medical Group La Verne

*see Various Departments*, California, United States

Compassionate Cancer Care Medical Group Dept.ofCCCMG

Fountain Valley, California, United States

Loma Linda University Dept.ofLomaLindaCancerCent(3)

Loma Linda, California, United States

University of California at Los Angeles Dept.of UCLA Dept.ofMed.

Los Angeles, California, United States

Florida Cancer Research Institute

Davie, Florida, 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

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

Cancer Centers of the Carolinas CC of C -Eastside

Greenville, South Carolina, United States

Sammons Cancer Center - Texas Oncology

Dallas, Texas, United States

Novartis Investigative Site

Charleroi, , Belgium

Novartis Investigative Site

Liège, , Belgium

Novartis Investigative Site

Turnhout, , Belgium

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Saint-Herblain Cédex, , France

Novartis Investigative Site

Toulouse, , France

Novartis Investigative Site

Villejuif, , France

Novartis Investigative Site

Maastricht, , Netherlands

Novartis Investigative Site

Lleida, Catalonia, Spain

Countries

United States; Belgium; France; Netherlands; Spain

Related Links

http://www.novartisclinicaltrials.com/etrials/searchTrial.do?trialID=712

Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

Other Identifiers

2006-001596-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRAD001J2101

Identifier Type: -

Identifier Source: org_study_id