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

Metastatic Breast Cancer Clinical Trial

Official title:

A Phase Ib/II Study Investigating the Combination of Everolimus With Trastuzumab and Paclitaxel in Patients With HER2-overexpressing Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00426556
• Other study ID #: CRAD001J2101
• Secondary ID: 2006-001596-37
• Status: Completed
• Phase: Phase 1
• First received: January 23, 2007
• Last updated: November 24, 2015
• Start date: July 2007
• Est. completion date: March 2014

Study information

• Verified date: November 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicines and Health Products, FAMHPFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Netherlands: Dutch Health Care InspectorateSpain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

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.
• 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
• 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.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Charleroi
Belgium	Novartis Investigative Site	Liege
Belgium	Novartis Investigative Site	Turnhout
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Saint-Herblain Cédex
France	Novartis Investigative Site	Toulouse Cedex 9
France	Novartis Investigative Site	Villejuif Cedex
Netherlands	Novartis Investigative Site	Maastricht
Spain	Novartis Investigative Site	Lleida	Cataluna
United States	Wilshire Oncology Medical Group La Verne	*see Various Departments*	California
United States	Emory University School of Medicine/Winship Cancer Institute Dept. of Hematology (2)	Atlanta	Georgia
United States	Sammons Cancer Center - Texas Oncology	Dallas	Texas
United States	Florida Cancer Research Institute	Davie	Florida
United States	North Shore University Health System	Evanston	Illinois
United States	Compassionate Cancer Care Medical Group Dept.ofCCCMG	Fountain Valley	California
United States	Cancer Centers of the Carolinas CC of C -Eastside	Greenville	South Carolina
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	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

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  France,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Phase I: Best Overall Response (BOR)	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.	every 8 - 9 weeks until disease progression or a new lesion is identified	No
Secondary	Phase II: Progression Free Survival (PFS)	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.	every 8 - 9 weeks until disease progression or a new lesion is identified	Yes
Secondary	Phase II: Overall Survival (OS)	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.	every 3 months until death	No

External Links

•   Breast Cancer