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

NCT00756717 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 200431
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer

Keywords

MK-0752; Tamoxifen; Letroxole

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing at Least One Adverse Event

  The number of participants experiencing at least one adverse event during the 24-day observation period and initial post-operative visit.

  30 days

Study Arms (1)

MK-0752

EXPERIMENTAL

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

Interventions

MK-0752 DRUG

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.

MK-0752

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Loyola University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center

Maywood, Illinois, 60153, United States

Location

Related Publications (1)

• Tabares-Seisdedos R, Rubenstein JL. Inverse cancer comorbidity: a serendipitous opportunity to gain insight into CNS disorders. Nat Rev Neurosci. 2013 Apr;14(4):293-304. doi: 10.1038/nrn3464.

  PMID: 23511909 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

3-(4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

There are no limitations or caveats to report.

Results Point of Contact

• Title: Dr. Kathy Albain
• Organization: Loyola University Medical Center

KALBAIN@lumc.edu

708-327-3102

Study Officials

• Kathy Albain, MD

  Loyola University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 19, 2008
• First Posted: September 22, 2008
• Study Start: February 14, 2008
• Primary Completion: December 21, 2011
• Study Completion: December 21, 2011
• Last Updated: September 4, 2019
• Results First Posted: September 4, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)