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

Advanced Breast Cancer Clinical Trial

Official title:

A Phase I Study of MK0752, a Notch Inhibitor, in Patients With Metastatic or Locally Advanced Breast Cancer and Other Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00106145
• Other study ID #: 0752-014
• Secondary ID: 2005_008
• Status: Completed
• Phase: Phase 1
• First received: March 21, 2005
• Last updated: January 29, 2015
• Start date: April 2005
• Est. completion date: August 2011

Study information

• Verified date: January 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms
• Other Solid Tumors

Intervention

Drug:
• Comparator: MK0752, Notch Inhibitor
Dose escalating beginning with rising dose levels of 300, 450, and 600 mg/day in a continuous dosing schedule.
• Comparator: MK0752, Notch Inhibitor - 450 mg
Dose 450 mg capsules daily for 28 day cycles.
• 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.
• 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.
• 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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Krop I, Demuth T, Guthrie T, Wen PY, Mason WP, Chinnaiyan P, Butowski N, Groves MD, Kesari S, Freedman SJ, Blackman S, Watters J, Loboda A, Podtelezhnikov A, Lunceford J, Chen C, Giannotti M, Hing J, Beckman R, Lorusso P. Phase I pharmacologic and pharmac — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability; MTD will be established		Day 1 to Day 28	Yes
Secondary	Overall tumor/disease response will be evaluated using RECIST criteria, radiographic and clinical evaluations		radigraphic evaluation = every 56 days	No