Clinical trial NCT00736970: Oral Deforolimus With Trastuzumab for Patients With HER2-positive Trastuzumab-Refractory Metastatic Breast Cancer (8669-009)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Breast Neoplasms
Keywords: ridaforolimus
deforolimus
AP23573
breast cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-08-18
Enrollment: 34
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR) measured by modified RECIST guidelines
timeFrame: Duration of the study
Secondary outcomes:
measure: Characterize the overall safety and tolerability of oral deforolimus administered in combination with standard dose trastuzumab
timeFrame: Duration of the study
measure: Evaluate the clinical-benefit response rate (CR or PR, or SD ≥ six 4-week cycles)
timeFrame: Throughout the trial
measure: Evaluate additional efficacy endpoints, such as duration of response, time to tumor progression, progression-free survival, progression free survival rate, and overall survival
timeFrame: Duration of the trial
measure: Perform exploratory molecular analyses
timeFrame: Duration of the trial
Other outcomes:
Locations:
Study officials:
References:
citation: Seiler M, Ray-Coquard I, Melichar B, Yardley DA, Wang RX, Dodion PF, Lee MA. Oral ridaforolimus plus trastuzumab for patients with HER2+ trastuzumab-refractory metastatic breast cancer. Clin Breast Cancer. 2015 Feb;15(1):60-5. doi: 10.1016/j.clbc.2014.07.008. Epub 2014 Aug 17.