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

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
First received: January 23, 2007
Last updated: January 7, 2015
Last verified: October 2014

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
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 l: To establish the feasible dose levels/regimens based on End-of-cycle-1 dose limiting toxicity rate. [ Time Frame: at every critical DLT, after 6 patients have completed cycle 1 or every 2 months ] [ Designated as safety issue: Yes ]
  • Phase II: To evaluate the efficacy of the dose/level regimen of RAD001 recommended from the phase I with trastuzumab and paclitaxel therapy. This will be based on the overall response rate. [ Time Frame: every 8 - 9 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase I : Assess ability to deliver trastuzumab and paclitaxel therapy based on the relative dose intensity of paclitaxel & on the discontinuation rate of trastuzumab, assess everolimus, trastuzumab & paclitaxel PK in a subset of patients [ Time Frame: every 8 - 9 weeks ] [ Designated as safety issue: No ]
  • To evaluate progression free survival (PFS), overall survival(OS) and to describe the safety profile of the phase II part combination. [ Time Frame: every 8 - 9 weeks and for OS, every 3 months ] [ Designated as safety issue: Yes ]

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: Everolimus Drug: everolimus
10 mg daily


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

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

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
Novartis Investigative Site
Charleroi, Belgium, 6000
Novartis Investigative Site
Liege, Belgium, 4000
Novartis Investigative Site
Turnhout, Belgium, 2300
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
Novartis Investigative Site
Maastricht, Netherlands, 6229 HX
Novartis Investigative Site
Lleida, Cataluña, Spain, 25198
Sponsors and Collaborators
Novartis Pharmaceuticals
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
Last Updated: January 7, 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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on March 26, 2015