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

Phase 2

Completed

• Conditions: Breast Cancer; Breast Neoplasms
• Interventions: Drug: ridaforolimus; Drug: trastuzumab

• Registration Number: NCT00736970
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-07
• Study First Submitted: 2008-08-14
• Study First Submitted QC: 2008-08-14
• Study First Posted: 2008-08-18
• Primary Completion: 2011-01
• Study Completion: 2011-05
• Status Verified: 2015-08
• Last Update Submitted: 2015-08-26
• Last Update Posted: 2015-08-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 34

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	ridaforolimus	10 mg oral tablets administered at 40 mg once daily for 5 consecutive days each week, followed by 2 days without ridaforolimus
1	trastuzumab	10 mg oral tablets administered at 40 mg once daily for 5 consecutive days each week, followed by 2 days without ridaforolimus

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) measured by modified RECIST guidelines	Duration of the study

Secondary Outcome Measures

Name	Time	Method
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