A Phase II Trial of Oral Deforolimus (AP23573; MK-8669), an mTOR Inhibitor, in Combination with Trastuzumab for Patients with HER2-positive Trastuzumab-Refractory Metastatic Breast Cancer

• Conditions: HER2-positive metastatic breast cancer; MedDRA version: 9.1Level: LLTClassification code 10027475Term: Metastatic breast cancer

• Registration Number: EUCTR2008-001971-30-CZ
• Lead Sponsor: Merck & Co, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-09-09
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 37

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 < 24 hours, and = 6 weeks for nitrosourea or mitomycin)
•Left ventricular ejection fraction of = 50%
•Adequate cardiovascular function (e.g., = class 2 New York Heart Association congestive heart failure, no myocardial infarction in the previous six months)
•Adequate haematological, hepatic and renal function as defined below:
•haemoglobin = 9 g/dL, absolute neutrophil counts [ANC] = 1.5 x 109 /L
•platelets = 100 x 109 /L
•bilirubin = ULN
•alkaline phosphatase = 2.5 x ULN
•AST, ALT = 2.5 x ULN; albumin = 2.5mg/dL; creatinine = 1.5 x ULN
•Serum cholesterol =350 mg/dL and triglycerides = 400 mg/dL
•Patients with childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of study drug and must use an approved contraceptive method as appropriate from time of study screening until 30 days after the last dose of study drug. Non-hormonal methods must be used in this trial. Approved contraceptive methods include, for example, intra-uterine device, diaphragm with spermicide, cervical cap with spermicide or female condom with spermicide. (Spermicides alone are not an acceptable method of contraception.)
•Availability and patient consent to obtain archival tumor tissue
•Signed informed consent document stating that the patient understands the investigational nature of the proposed treatment

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified