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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00426556
First received: January 23, 2007
Last updated: April 2, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: Everolimus
Drug: Trastuzumab
Drug: Paclitaxel
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study Investigating the Combination of Everolimus With Trastuzumab and Paclitaxel in Patients With HER2-overexpressing Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Phase II: Overall Response Rate [ Time Frame: every 8 - 9 weeks until disease progression or a new lesion is identified ] [ Designated as safety issue: No ]
    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:
  • Phase I: Best Overall Response (BOR) [ Time Frame: every 8 - 9 weeks until disease progression or a new lesion is identified ] [ Designated as safety issue: No ]
    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) [ Time Frame: every 8 - 9 weeks until disease progression or a new lesion is identified ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: every 3 months until death ] [ Designated as safety issue: No ]
    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.


Enrollment: 88
Study Start Date: July 2007
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I - RAD001 5mg + PT, daily
Daily dosing schedule of EPT = Paclitaxel & Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab.
Drug: 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.
Other Name: RAD001
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
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.
Experimental: Phase I - RAD001 10mg + PT, daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
Drug: 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.
Other Name: RAD001
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
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.
Experimental: Phase I - RAD001 30mg + PT, weekly
Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab.
Drug: 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.
Other Name: RAD001
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
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.
Experimental: Phase II - RAD001 10mg + PT, daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
Drug: 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.
Other Name: RAD001
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
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00426556

Locations
United States, California
Wilshire Oncology Medical Group La Verne
*see Various Departments*, California, United States
Compassionate Cancer Care Medical Group Dept.ofCCCMG
Fountain Valley, California, United States, 92708
Loma Linda University Dept.ofLomaLindaCancerCent(3)
Loma Linda, California, United States, 92354
University of California at Los Angeles Dept.of UCLA Dept.ofMed.
Los Angeles, California, United States, 90095
United States, Florida
Florida Cancer Research Institute
Davie, Florida, United States, 33328
United States, Georgia
Emory University School of Medicine/Winship Cancer Institute Dept. of Hematology (2)
Atlanta, Georgia, United States, 30322
United States, Illinois
North Shore University Health System
Evanston, Illinois, United States, 60201
United States, Maryland
Peninsula Regional Medical Center Deptof Oncology and Hematology
Salisbury, Maryland, United States, 21801
United States, Missouri
Washington University School Of Medicine-Siteman Cancer Ctr StudyCoordinator:CRAD001J2101
St. Louis, Missouri, United States, 63110
United States, South Carolina
Cancer Centers of the Carolinas CC of C -Eastside
Greenville, South Carolina, United States, 29605
United States, Texas
Sammons Cancer Center - Texas Oncology
Dallas, Texas, United States, 78246
Belgium
Novartis Investigative Site
Charleroi, Belgium, 6000
Novartis Investigative Site
Liege, Belgium, 4000
Novartis Investigative Site
Turnhout, Belgium, 2300
France
Novartis Investigative Site
Paris, France, 75970
Novartis Investigative Site
Saint-Herblain Cédex, France, 44805
Novartis Investigative Site
Toulouse Cedex 9, France, 31059
Novartis Investigative Site
Villejuif Cedex, France, 94805
Netherlands
Novartis Investigative Site
Maastricht, Netherlands, 6229 HX
Spain
Novartis Investigative Site
Lleida, Cataluna, Spain, 25198
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00426556     History of Changes
Other Study ID Numbers: CRAD001J2101, 2006-001596-37
Study First Received: January 23, 2007
Results First Received: March 20, 2015
Last Updated: April 2, 2015
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Netherlands: Dutch Health Care Inspectorate
Spain: Spanish Agency of Medicines

Keywords provided by Novartis:
Breast cancer
Cancer of the breast
Human mammary carcinoma
HER-2
Metastatic
everolimus
trastuzumab
paclitaxel

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Everolimus
Paclitaxel
Sirolimus
Trastuzumab
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on April 23, 2015