This trial is active, not recruiting.

Condition breast cancer
Treatments everolimus, placebo
Phase phase 3
Targets mTOR, FKBP-12
Sponsor Novartis Pharmaceuticals
Start date September 2009
End date January 2017
Trial size 719 participants
Trial identifier NCT00876395, 2008-006556-21, CRAD001J2301


The purpose of this Phase III study is to confirm the value of adding everolimus to weekly paclitaxel and trastuzumab as treatment of HER2-overexpressing metastatic breast cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22
everolimus RAD001
(Placebo Comparator)
Placebo of everolimus daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22

Primary Outcomes

Progression-free Survival (PFS)
time frame: Every 8 weeks

Secondary Outcomes

Overall Survival (OS)
time frame: Every 3 months
Overall response rate (ORR)
time frame: Every 8 weeks
Clinical benefit rate (CBR)
time frame: Every 8 weeks
Time to overall response (Complete reseponse (CR) or partial response (PR) )
time frame: Every 8 weeks
Overall Response(OR)
time frame: Every 8 weeks
Blood levels at steady states for everolimus/placebo
time frame: Cycle 2/Day 1, Cycle 2/Day 15, Cycle 2/ Day 22, Cycle 4/Day 1
time frame: Continuous and every 8 weeks while on trial, 30 day safety update after last dose of study drug

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Adult Women (≥ 18 years old). - Histologically or cytologically confirmed invasive breast carcinoma with local recurrence or radiological evidence of metastatic disease. - Must have at least one lesion that can be accurately measured or bone lesions in the absence of measurable disease. - HER2+ patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive). - Prior trastuzumab and/or chemotherapy (taxanes included) as neo-adjuvant or adjuvant treatment is allowed but should be discontinued > 12 months prior to randomization. - Prior treatment for breast cancer with endocrine therapy (adjuvant or metastatic settings) is allowed but should be discontinued at randomization. Patients treated with bisphosphonates at entry or who start bisphosphonates during study may continue this therapy during protocol treatment. - Documentation of negative pregnancy test. Exclusion Criteria: - Prior mTOR inhibitors for the treatment of cancer. - Other anticancer therapy for locally advanced or metastatic breast cancer except for prior hormonal therapy. - Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites, etc). - Radiotherapy to ≥ 25% of the bone marrow within 4 weeks prior to randomization - History of central nervous system metastasis. - Impairment of gastrointestinal (GI) function or GI disease or active ulceration of the upper gastrointestinal tract. - Serious peripheral neuropathy. - Cardiac disease or dysfunction. - Uncontrolled hypertension. - HIV. - Pregnant, Other protocol-defined inclusion/exclusion criteria may apply

Additional Information

Official title A Randomized Phase III, Double-Blind, Placebo-Controlled Multicenter Trial of Everolimus in Combination With Trastuzumab and Paclitaxel, as First Line Therapy in Women With HER2 Positive Locally Advanced or Metastatic Breast Cancer
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Novartis.
Location data was received from the National Cancer Institute and was last updated in August 2016.