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 (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00736970
First received: August 14, 2008
Last updated: September 17, 2014
Last verified: September 2014
  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:


Further study details as provided by Merck Sharp & Dohme Corp.:

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00736970     History of Changes
Other Study ID Numbers: 8669-009, AP23573-08-207
Study First Received: August 14, 2008
Last Updated: September 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
ridaforolimus
deforolimus
AP23573
breast cancer

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

ClinicalTrials.gov processed this record on September 18, 2014