The Growth Factor Signature (GFS) as an Intermediate Biomarker of Response for Development of PI3K-Pathway Inhibitors in Patients With Breast Cancer (MK-8669-050)

Study Overview
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Brief Summary
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This clinical trial will evaluate whether treatment with ridaforolimus, dalotuzumab, or ridforolimus/dalotuzumab combination therapy reduces Growth Factor Signature (GFS) Score among participants with breast cancer.

Official Title
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A Clinical Trial to Qualify the Growth Factor Signature (GFS) as an Intermediate Biomarker of Response for Development of PI3K-Pathway Inhibitors in Patients With Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Ridaforolimus + Dalotuzumab
* Drug: Ridaforolimus
* Drug: Dalotuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has operable Stage I-IIIa invasive breast cancer of the following subtype: ER-positive, HER2-negative tumor with histologic grade 2 or 3 and Ki67 ≥ 15% Tumor is at least 2 cm in diameter as assessed by physical or radiographic exam Participant consents to provide an existing tissue sample or to have a core needle biopsy before drug administration Participant consents to provide tissue samples following drug administration by a second core needle biopsy or from a surgical specimen Participant must have adequate organ function Exclusion Criteria: Participant has received any prior chemotherapy, biological therapy or radiotherapy for breast cancer Participant has a known hypersensitivity to the components of study drugs or their analogs, including hypersensitivity to macrolide antibiotics (e.g. clarithromycin, erythromycin, azithromycin). Participant has poorly controlled diabetes mellitus, or requires insulin for glucose control. Participant is unable to swallow capsules and/or absorb oral medications Participant is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study. Participant is known to be Human Immunodeficiency Virus (HIV)-positive Participant has known history of active Hepatitis B or C. Participant is concurrently using growth hormone (GH) or growth hormone inhibitors Participant has significant or uncontrolled cardiovascular disease, including heart failure, unstable angina, or a myocardial infarction within the last 6 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ridaforolimus + Dalotuzumab<br>Ridaforolimus (MK-8669) + Dalotuzumab (MK-0646) | Drug: Ridaforolimus + Dalotuzumab<br>* Ridaforolimus (MK-8669) once daily for 5 consecutive days per week and Dalotuzumab (MK-0646) intravenously (IV) once weekly for 2 weeks<br>* Other names: MK-8669, MK-0646;|
| Experimental: Ridaforolimus<br>Ridaforolimus (MK-8669) | Drug: Ridaforolimus<br>* Ridaforolimus 40 mg (once daily for 5 consecutive days per week) for 2 weeks, 10 mg enteric-coated tablets<br>* Other names: MK-8669;|
| Experimental: Dalotuzumab<br>Dalotuzumab (MK-0646) | Drug: Dalotuzumab<br>* Dalotuzumab, intravenously (IV) at 10 mg/kg/week for 2 weeks<br>* Other names: MK-0646;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The population mean change from baseline in GFS (Growth Factor Signature) score |  | Baseline and Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The population mean change from baseline in Ki67 among participants receiving ridaforolimus/dalotuzumab combination therapy |  | Baseline and Day 15 | 
| The correlation between change in Ki67 expression and change in GFS after two weeks of treatment with ridaforolimus/dalotuzumab (MK-8669/MK-0646) combination therapy, ridaforolimus (MK-8669) monotherapy and/or dalotuzumab (MK-0646) monotherapy |  | Baseline and Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, ridaforolimus, ridaforolimus/dalotuzumab combination therapy