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

This study has been completed.
Sponsor:
Information provided by:
Merck
ClinicalTrials.gov Identifier:
NCT00736970
First received: August 14, 2008
Last updated: July 7, 2011
Last verified: July 2011
History of Changes
  Purpose

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 Intervention Phase
Breast Cancer
Breast Neoplasms
 Drug: ridaforolimus
Drug: trastuzumab
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Drug Information available for: Trastuzumab
U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:
  • Objective Response Rate (ORR) measured by modified RECIST guidelines [ Time Frame: Duration of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Characterize the overall safety and tolerability of oral deforolimus administered in combination with standard dose trastuzumab [ Time Frame: Duration of the study ] [ Designated as safety issue: Yes ]
  • Evaluate the clinical-benefit response rate (CR or PR, or SD ≥ six 4-week cycles) [ Time Frame: Throughout the trial ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Perform exploratory molecular analyses [ Time Frame: Duration of the trial ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: July 2008
Study Completion Date: May 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier: NCT00736970     History of Changes
Other Study ID Numbers: MK-8669-009, AP23573-08-207
Study First Received: August 14, 2008
Last Updated: July 7, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck:
ridaforolimus
deforolimus
AP23573
breast cancer

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

ClinicalTrials.gov processed this record on May 22, 2013