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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00736970
Recruitment Status : Completed
First Posted : August 18, 2008
Last Update Posted : August 27, 2015
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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 Type : Interventional  (Clinical Trial)
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 : July 2008
Actual Primary Completion Date : January 2011
Actual Study Completion Date : May 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Trastuzumab
U.S. FDA Resources

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 Name: Herceptin

Primary Outcome Measures :
  1. Objective Response Rate (ORR) measured by modified RECIST guidelines [ Time Frame: Duration of the study ]

Secondary Outcome Measures :
  1. Characterize the overall safety and tolerability of oral deforolimus administered in combination with standard dose trastuzumab [ Time Frame: Duration of the study ]
  2. Evaluate the clinical-benefit response rate (CR or PR, or SD ≥ six 4-week cycles) [ Time Frame: Throughout the trial ]
  3. Evaluate additional efficacy endpoints, such as duration of response, time to tumor progression, progression-free survival, progression free survival rate, and overall survival [ Time Frame: Duration of the trial ]
  4. Perform exploratory molecular analyses [ Time Frame: Duration of the trial ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Publications of Results:
Responsible Party: Merck Sharp & Dohme Corp. Identifier: NCT00736970     History of Changes
Other Study ID Numbers: 8669-009
AP23573-08-207 ( Other Identifier: Secondary ID )
First Posted: August 18, 2008    Key Record Dates
Last Update Posted: August 27, 2015
Last Verified: August 2015

Keywords provided by Merck Sharp & Dohme Corp.:
breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs