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

Study Overview
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Brief Summary
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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.

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

Conditions
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Advanced Breast Cancer, Other Solid Tumors

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part I - Arm 1<br> | Drug: Comparator: MK0752, Notch Inhibitor<br>* Dose escalating beginning with rising dose levels of 300, 450, and 600 mg/day in a continuous dosing schedule.<br>|
| Experimental: Part II - Arm 1<br> | Drug: Comparator: MK0752, Notch Inhibitor - 450 mg<br>* Dose 450 mg capsules daily for 28 day cycles.<br>|
| Experimental: Part III - Arm 1<br> | Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off<br>* 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.<br>|
| Experimental: Part IV - Arm 1<br> | Drug: Comparator: MK0752, Notch Inhibitor - 1 day on, 6 off<br>* 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.<br>|
| Experimental: Part V - Arm 1<br> | Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off 350 mg<br>* Dose 350 mg capsules daily intermittent 3 days on/4 days off dosing. THIS DOSING SCHEDULE IS NO LONGER UNDER INVESTIGATION<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability; MTD will be established |  | Day 1 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall tumor/disease response will be evaluated using RECIST criteria, radiographic and clinical evaluations |  | radigraphic evaluation = every 56 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Breast Cancer, Solid Tumors, Advanced Solid Tumors