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

A Pilot Study of MK-0752 in Combination With Tamoxifen or Letrozole in Patients With Early Stage Breast Cancer Prior to Surgery

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: MK-0752

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MK-0752; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Loyola University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Kathy Albain, MD, Loyola University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2008
• Primary Completion (Actual): December 21, 2011
• Study Completion (Actual): December 21, 2011

Study Registration Dates

• First Submitted: September 19, 2008
• First Submitted That Met QC Criteria: September 19, 2008
• First Posted (Estimate): September 22, 2008

Study Record Updates

• Last Update Posted (Actual): September 4, 2019
• Last Update Submitted That Met QC Criteria: August 14, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Tamoxifen; MK-0752; Letroxole
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 200431

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no plan to make individual participant data available to other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No