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

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT00736970

Collaborator

(none)

Enrollment

Arm

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Breast Neoplasms	Drug: ridaforolimus Drug: trastuzumab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jul 1, 2008

Actual Primary Completion Date :

Jan 1, 2011

Actual Study Completion Date :

May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 10 mg oral tablets administered at 40 mg once daily for 5 consecutive days each week, followed by 2 days without ridaforolimus	Drug: ridaforolimus 10 mg oral tablets administered at 40 mg once daily for 5 consecutive days each week, followed by 2 days without ridaforolimus. Other Names: deforolimus AP23573 MK-8669 ridaforolimus was also known as deforolimus until May 2009 Drug: trastuzumab single intravenous infusion every week; initial dose of 4 mg/kg over 90 minutes, then 2 mg/kg over 30 minutes Other Names: Herceptin

Arm

Intervention/Treatment

Experimental: 1

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

Drug: ridaforolimus

10 mg oral tablets administered at 40 mg once daily for 5 consecutive days each week, followed by 2 days without ridaforolimus.

Other Names:

deforolimus

AP23573

MK-8669

ridaforolimus was also known as deforolimus until May 2009

Drug: trastuzumab

single intravenous infusion every week; initial dose of 4 mg/kg over 90 minutes, then 2 mg/kg over 30 minutes

Other Names:

Herceptin

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) measured by modified RECIST guidelines [Duration of the study]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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