Study Of MK-0752 In Combination With Tamoxifen Or Letrozole to Treat Early Stage Breast Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2011 by Loyola University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
Loyola University
ClinicalTrials.gov Identifier:
NCT00756717
First received: September 19, 2008
Last updated: July 14, 2011
Last verified: March 2011
  Purpose

The purpose of this research project is to study the effect of a research (investigational) drug, MK-0752 combined with either tamoxifen or letrozole on breast cancer cells.

Tamoxifen and letrozole are standard hormone treatments used to treat breast cancers that are positive for the estrogen receptor. However, over time the breast cancer cells can become resistant to tamoxifen and letrozole. MK-0752 is in a class of drugs called gamma secretase inhibitors. Gamma secretase inhibitors may play a role in reversing the resistance to drugs such as tamoxifen and letrozole.


Condition Intervention
Breast Cancer
Drug: MK-0752

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Pilot Study of MK-0752 in Combination With Tamoxifen or Letrozole in Patients With Early Stage Breast Cancer Prior to Surgery

Resource links provided by NLM:


Further study details as provided by Loyola University:

Primary Outcome Measures:
  • To evaluate the safety and tolerability of the gamma-secretase inhibitor MK-0752 in the pre-surgical setting in patients with early stage, estrogen receptor (ER) positive breast cancer, in combination with tamoxifen or an aromatase inhibitor (AI). [ Time Frame: Treatment will be given over a 24 day period. Toxcity assessments will be done on or around day 15, day 25 and at the post surgical visit. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To establish the feasibility and success of multi-laboratory collaborations in evaluating clinical specimens and biomarker testing [ Time Frame: Completion of study ] [ Designated as safety issue: No ]
  • To provide preliminary data on the impact of MK-0752 on the panel of biomarkers under investigation. [ Time Frame: Completion of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: May 2008
Estimated Study Completion Date: January 2012
Estimated Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
oral gamma-secretase inhibitor drug MK-0752, 350 mg for three days, four days off, then three days on, over a period of 10 days
Drug: MK-0752
Women who are post menopausal will receive letrozole 2.5 mg by mouth one time per day for 24 days. Women who are pre menopausal, or who have a contraindication to letrozole will receive tamoxifen 20 mg orally one time per day for a period of 24 days. Starting on day 15 of this 24 day period all patients will receive the oral gamma-secretase inhibitor drug MK-0752 at a dose of 350 mg for three days on, then off four days, then three days on, for a total of 6 doses over a period of 10 days.

Detailed Description:

OBJECTIVES

To evaluate the safety and tolerability of the gamma-secretase inhibitor MK-0752 in the pre-surgical setting in patients with early stage, estrogen receptor (ER) positive breast cancer, in combination with tamoxifen or an aromatase inhibitor (AI).

To establish the feasibility and success of multi-laboratory collaborations in evaluating clinical specimens and biomarker testing.

To provide preliminary data on the impact of MK-0752 on a panel of biomarkers involved in the notch signaling pathway.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed early stage, ER-positive (Allred score ≥3), invasive breast cancer that is not either locally advanced by criteria other than size or inflammatory, and is not metastatic. - Patients must be candidates for surgical removal of the tumor by lumpectomy or mastectomy.
  • Patients must not have bilateral tumors. Tumor must be amenable to core biopsy in midstudy.
  • Patients must be >18 years of age.
  • Patients must have a performance status ≤1 by Zubrod criteria.
  • Patients must have a life expectancy of greater than three months.
  • Patients must have normal organ and marrow function within 28 days of registration as defined below:

    • absolute neutrophil count >1,500/μL
    • platelets >100,000/μL
    • total bilirubin ≤1.5 x the institutional upper limit of normal
    • AST(SGOT)/ALT(SGPT) <2 X institutional upper limit of normal
    • creatinine within normal institutional limits OR
    • creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. A negative serum pregnancy test must be obtained within 72 hours of receiving the first dose of the hormonal therapy as well as within 72 hours of the first dose of the MK-0752 GSI medication for women of child-bearing potential. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

  • Patients may not have received any prior chemotherapy or endocrine therapy (tamoxifen, raloxifene, or an aromatase inhibitor) and may not have received prior therapy with a gamma-secretase inhibitor or other investigational agents. - Patients may not have received previous radiation therapy.
  • Patients may not be currently participating or have participated in a study with an investigational compound or device within 30 days.
  • Patients must not have known brain or CNS disease, evidence of brain or CNS metastases, or carcinomatous meningitis.
  • Patients must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients may not have known hypersensitivity to the components of MK-0752 or it analogs.
  • Patients will be excluded if there is a known history of human immunodeficiency (HIV) virus infection, or a known history of hepatitis B or C infection.
  • Patients must not have a previous history of inflammatory bowel disease or uncontrolled irritable bowel syndrome.
  • Patients must not have a history of greater than one basal cell carcinoma of the skin within the past five years or a history of Gorlin syndrome.
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00756717

Locations
United States, Illinois
Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center
Maywood, Illinois, United States, 60153
Sponsors and Collaborators
Loyola University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Kathy Albain, MD Loyola University
  More Information

No publications provided by Loyola University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kathy Albain MD, Loyola University
ClinicalTrials.gov Identifier: NCT00756717     History of Changes
Other Study ID Numbers: 200431
Study First Received: September 19, 2008
Last Updated: July 14, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Loyola University:
MK-0752
Tamoxifen
Letroxole

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Letrozole
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Selective Estrogen Receptor Modulators
Bone Density Conservation Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 29, 2014