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

Novartis Pharmaceuticals88 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Metastatic Breast Cancer

Interventions

EverolimusDRUG

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.

TrastuzumabDRUG

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

PaclitaxelDRUG

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (20)

Wilshire Oncology Medical Group La Verne

*see Various Departments*, California, United States

Outcomes

Primary Outcomes

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.

Time frame: every 8 - 9 weeks until disease progression or a new lesion is identified

Secondary Outcomes

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.

Time frame: every 8 - 9 weeks until disease progression or a new lesion is identified

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.

Data from ClinicalTrials.gov

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