A Notch Signalling Pathway Inhibitor for Patients With Advanced Breast Cancer (0752-014)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00106145
First received: March 21, 2005
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

An investigational study to determine the safety/tolerability, and efficacy of a notch signaling pathway inhibitor in patients with metastatic or locally advanced breast cancer and other advanced solid tumors.


Condition Intervention Phase
Advanced Breast Cancer
Other Solid Tumors
Drug: Comparator: MK0752, Notch Inhibitor
Drug: Comparator: MK0752, Notch Inhibitor - 450 mg
Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off
Drug: Comparator: MK0752, Notch Inhibitor - 1 day on, 6 off
Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off 350 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of MK0752, a Notch Inhibitor, in Patients With Metastatic or Locally Advanced Breast Cancer and Other Solid Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Safety and tolerability; MTD will be established [ Time Frame: Day 1 to Day 28 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall tumor/disease response will be evaluated using RECIST criteria, radiographic and clinical evaluations [ Time Frame: radigraphic evaluation = every 56 days ] [ Designated as safety issue: No ]

Enrollment: 103
Study Start Date: April 2005
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part I - Arm 1 Drug: Comparator: MK0752, Notch Inhibitor
Dose escalating beginning with rising dose levels of 300, 450, and 600 mg/day in a continuous dosing schedule.
Experimental: Part II - Arm 1 Drug: Comparator: MK0752, Notch Inhibitor - 450 mg
Dose 450 mg capsules daily for 28 day cycles.
Experimental: Part III - Arm 1 Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off
Dose escalating in a repeating intermittent dosing schedule of 3 days on and 4 days off at rising dose levels of 450, 600, 800, 1000, 1200, and 1400 mg/day.
Experimental: Part IV - Arm 1 Drug: Comparator: MK0752, Notch Inhibitor - 1 day on, 6 off
Dose escalating in a repeating intermittent dosing schedule of 1 day on/6 days off at rising dose levels of 600, 900, 1200, 1500, 1800, 2400, 3200 mg/day once weekly and then increase at 33% increments.
Experimental: Part V - Arm 1 Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off 350 mg
Dose 350 mg capsules daily intermittent 3 days on/4 days off dosing. THIS DOSING SCHEDULE IS NO LONGER UNDER INVESTIGATION

  Eligibility

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

Inclusion Criteria:

  • Women or men greater than or equal to 18 years of age
  • ECOG status less than or equal to 2 (a measurement to determine your ability to perform daily activities)
  • In Parts I, III, and IV, patient must have a histologically confirmed, metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. There is no limit on the number of prior treatment regimens
  • In Part II, only breast cancer patients are eligible
  • In Part V, only patients with Numb negative breast cancer (i.e., tumor shows Numb immunoreactivity in less than 10% of the neoplastic cells assessed) are eligible
  • Patient has recovered from and is at least 2 weeks from previous antineoplastic therapy, including chemotherapy, biological therapy (including Herceptin), hormonal therapy, radiotherapy, or surgery

Exclusion Criteria:

  • Patient has had an investigational treatment in the preceding 21 days
  • Uncontrolled congestive heart failure or myocardial infarction (heart attack) within 3 months of study start
  • History of hepatitis B or C or HIV
  • Patient has the presence of clinically apparent central nervous system metastases or carcinomatous meningitis. Patients with CNS metastases who have completed a course of radiotherapy and are clinically stable in the judgment of the investigator are eligible
  • Patients with "currently active" second malignancy, other than non-melanoma skin cancer, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for prior malignancy and are considered by their physician to be at <30% risk of relapse
  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: NCT00106145

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00106145     History of Changes
Other Study ID Numbers: 0752-014, 2005_008
Study First Received: March 21, 2005
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Advanced Breast Cancer
Solid Tumors
Advanced Solid Tumors

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on September 30, 2014