Clinical trial NCT00106145: A Notch Signalling Pathway Inhibitor for Patients With Advanced Breast Cancer (0752-014)
Official title: A Phase I Study of MK0752, a Notch Inhibitor, in Patients With Metastatic or Locally Advanced Breast Cancer and Other Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Breast Cancer
Other Solid Tumors
Keywords: Advanced Breast Cancer
Solid Tumors
Advanced Solid Tumors
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2005-03-22
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Safety and tolerability; MTD will be established
timeFrame: Day 1 to Day 28
Secondary outcomes:
measure: Overall tumor/disease response will be evaluated using RECIST criteria, radiographic and clinical evaluations
timeFrame: radigraphic evaluation = every 56 days
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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 pharmacodynamic study of the gamma secretase (Notch) inhibitor MK-0752 in adult patients with advanced solid tumors. J Clin Oncol. 2012 Jul 1;30(19):2307-13. doi: 10.1200/JCO.2011.39.1540. Epub 2012 Apr 30.