Breast Cancer, Breast Neoplasms
Conditions
Keywords
ridaforolimus, deforolimus, AP23573, breast cancer
Brief summary
This clinical trial will study the use of ridaforolimus in metastatic breast cancer subjects whose tumors have shown a resistance to trastuzumab (herceptin). The goal of this study is to find out if subjects treated with ridaforolimus in combination with trastuzumab have a positive response to the treatment, and if treatment with ridaforolimus in combination with trastuzumab prolongs survival.
Interventions
DRUGridaforolimus
10 mg oral tablets administered at 40 mg once daily for 5 consecutive days each week, followed by 2 days without ridaforolimus.
DRUGtrastuzumab
single intravenous infusion every week; initial dose of 4 mg/kg over 90 minutes, then 2 mg/kg over 30 minutes
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female, 18 years of age or older * Histologically confirmed HER2-positive metastatic breast cancer * Trastuzumab-resistance * Measurable disease, according to RECIST guidelines * ECOG performance status less than or equal to 1 * Life expectancy greater than 3 months * No prior treatment with temsirolimus, everolimus, rapamycin, or any other mTOR inhibitor * At least 4 weeks must have lapsed between prior investigational therapy, chemotherapy or radiotherapy, and the first dose of ridaforolimus * Left ventricular ejection greater than or equal to 50% * Adequate cardiovascular function * Adequate hematological, hepatic, and renal function * Serum cholesterol less than or equal to 350 mg/dL and triglycerides less than or equal to 400 mg/dL * Negative pregnancy test within 7 days prior to first dose of study drug and must use an approved contraceptive method from screening to 30 days after the last dose of study drug * Availability and patient consent to obtain archival tissue samples * Signed informed consent
Exclusion criteria
* Inadequate recovery from any prior surgical procedure or having undergone any major surgery within 2 weeks before trial entry * Grade 1 or Grade 2 hypersensitivity reactions to prior trastuzumab therapy if these reactions prevented further trastuzumab administration * Grade 3 or Grade 4 hypersensitivity reaction to prior trastuzumab * Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest * Known allergy to macrolide antibiotics * Pregnant or breast-feeding * Know history of HIV * Diagnosis of brain metastasis or leptomeningeal carcinomatosis within 3 months * Other malignancies within the past 3 years, except for adequately treated carcinoma of the cervix or basal or squamous cell carcinoma of the skin * Active infection requiring prescription intervention * Newly diagnosed or poorly controlled Type 1 or 2 diabetes * Other concurrent illness which, in the Investigator's judgment, would either compromise the patient's safety or interfere with the evaluation of the safety of the study drug * Concurrent treatment with medications that strongly induce or inhibit cytochrome P450. * Any condition that renders patient unable to fully understand and provide informed consent and/or comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) measured by modified RECIST guidelines | Duration of the study |
Secondary
| Measure | Time frame |
|---|---|
| Characterize the overall safety and tolerability of oral deforolimus administered in combination with standard dose trastuzumab | Duration of the study |
| Evaluate the clinical-benefit response rate (CR or PR, or SD ≥ six 4-week cycles) | Throughout the trial |
| Evaluate additional efficacy endpoints, such as duration of response, time to tumor progression, progression-free survival, progression free survival rate, and overall survival | Duration of the trial |
| Perform exploratory molecular analyses | Duration of the trial |
Outcome results
None listed