Oral Deforolimus With Trastuzumab for Patients With HER2-positive Trastuzumab-Refractory Metastatic Breast Cancer (8669-009)

Study Overview
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Brief Summary
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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.

Official Title
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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
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Breast Cancer, Breast Neoplasms

Intervention / Treatment
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* Drug: ridaforolimus
* Drug: trastuzumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>10 mg oral tablets administered at 40 mg once daily for 5 consecutive days each week, followed by 2 days without ridaforolimus | Drug: ridaforolimus<br>* 10 mg oral tablets administered at 40 mg once daily for 5 consecutive days each week, followed by 2 days without ridaforolimus.<br>* Other names: ridaforolimus was also known as deforolimus until May 2009;Drug: trastuzumab<br>* single intravenous infusion every week; initial dose of 4 mg/kg over 90 minutes, then 2 mg/kg over 30 minutes<br>* Other names: Herceptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) measured by modified RECIST guidelines |  | Duration of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ridaforolimus, deforolimus, AP23573, breast cancer