HER2-positive metastatic breast cancer MedDRA version: 9.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer
Conditions
Sponsors
Merck & Co, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Female patients, age = 18 yrs •Histologically confirmed HER-2 positive (IHC 3+ or FISH+) metastatic breast cancer (MBC) •Trastuzumab-resistance, defined as disease progression on trastuzumab treatment, with at most 2 prior trastuzumab-based regimens permitted •Either combination or single-agent trastuzumab treatment acceptable •Maintenance after combination therapy considered part of that overall regimen (i.e., will be counted as one regimen) •Single-agent trastuzumab therapy (without disease progression) followed by combination trastuzumab therapy acceptable at the time of disease progression. •Adjuvant trastuzumab-containing therapy permitted and will count as one regimen •Measurable disease according to modified RECIST guidelines (histological/cytological confirmation of the neoplastic nature of a solitary lesion is not required in this trial) •ECOG performance status = 1 •Life expectancy > 3 months •No prior treatment with temsirolimus, everolimus, rapamycin, or any other mTOR inhibitor •At least 4 weeks much have elapsed between prior investigational therapy, chemotherapy or radiotherapy, and the first dose of deforolimus (=2 weeks for signal transduction inhibitors with a half-life known to be =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Inadequate recovery from any prior surgical procedure or having undergone any major surgery within 2 weeks before trial entry (with the exception of minor procedures, e.g., central venous access port placement) •Grade 1 or Grade 2 hypersensitivity reaction to prior trastuzumab therapy if these reactions prevented further trastuzumab administration •Grade 3 or Grade 4 hypersensitivity reaction to prior trastuzumab •Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest •Known allergy to macrolide antibiotics •Pregnant or breast-feeding •Known history of HIV sero-positivity •Diagnosis of brain metastasis or leptomeningeal carcinomatosis within 3 months, and/or active brain metastases or leptomeningeal carcinomatosis, including those requiring glucocoricoid treatment •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 prescribed intervention •Newly diagnosed (within 3 months before enrolment) or poorly controlled Type 1 or 2 diabetes •Newly diagnosed (within 3 months or before enrolment) 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 (CYP3A). Patients should be off these medications = 2 weeks prior to the first dose of deforolimus. Concomitant medications that are metabolied by CYP3A are allowed (e.g., atorvastatin or simvastatin) •Any condition in the Investigator’s judgement that renders the patient unable to fully understand and provide informed consent and/or comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess the objective response rate by RECIST guidelines of oral deforolimus in combination with trastuzumab in patients with HER2-positive metastatic breast cancer (MBC) with progression after treatment with at most 2 prior trastuzumab-based regimens.;Primary end point(s): Objective response rate by modified RECIST guidelines;Secondary Objective: •Characterize safety and tolerability of oral deforolimus administered in combo with std dose trastuzumab •Evaluate the clinical-benefit response rate (CR or PR, SD = six 4-wk cycles) •Evaluate addtn'l efficacy endpts, (e.g. duration of response, time to tumor progression, pfs, pfs rate, os). •Perform a series of exploratory molecular analyses such as: •Exploratory analysis of molecular parameters in archival tumor samples for predictive/indicative ability of mTOR inhibition impacting trastuzumab resistance (e.g. markers of tumoral PI3K/mTOR-pathway activity and related pathways). Possible analysis of the mutational/expression/activation status of specific genes (e.g. PI3CA; PTEN, p95HER2 and IGF-1R) or gene expression profiling for status of entire signaling pathways •Exploratory analysis of pre-/post-treatment changes in circulating tumor cells and their expression of certain HER2 and PI3K/mTOR pathway-related changes pending evolving technology | — |
Countries
Czech Republic, France
Outcome results
None listed