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

January 23, 2007
April 2, 2015
July 2007
March 2014   (final data collection date for primary outcome measure)
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.
To establish the feasible dose levels/regimens based on end-of-cycle-1 dose limiting toxicity
Complete list of historical versions of study NCT00426556 on ClinicalTrials.gov Archive Site
  • 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.
  • To assess the ability to deliver the trastuzumab and paclitaxel therapy
  • To assess everolimus, trastuzumab and paclitaxel blood levels in this combination
  • To evaluate the overall tumor response
Not Provided
Not Provided
 
Efficacy and Safety of Everolimus in Combination Therapy, in Patients With HER2-overexpressing Metastatic Breast Cancer
A Phase Ib/II Study Investigating the Combination of Everolimus With Trastuzumab and Paclitaxel in Patients With HER2-overexpressing Metastatic Breast Cancer

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Metastatic Breast Cancer
  • 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 5mg + PT, daily
    Daily dosing schedule of EPT = Paclitaxel & Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab.
    Interventions:
    • Drug: Everolimus
    • Drug: Trastuzumab
    • Drug: Paclitaxel
  • Experimental: Phase I - RAD001 10mg + PT, daily
    Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
    Interventions:
    • Drug: Everolimus
    • Drug: Trastuzumab
    • Drug: Paclitaxel
  • Experimental: Phase I - RAD001 30mg + PT, weekly
    Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab.
    Interventions:
    • Drug: Everolimus
    • Drug: Trastuzumab
    • Drug: Paclitaxel
  • Experimental: Phase II - RAD001 10mg + PT, daily
    Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
    Interventions:
    • Drug: Everolimus
    • Drug: Trastuzumab
    • Drug: Paclitaxel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
88
March 2014
March 2014   (final data collection date for primary outcome measure)

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

Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   France,   Netherlands,   Spain
 
NCT00426556
CRAD001J2101, 2006-001596-37
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP