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)

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT01220570

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Ridaforolimus + Dalotuzumab Drug: Ridaforolimus Drug: Dalotuzumab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

63 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2010

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Ridaforolimus + Dalotuzumab

Ridaforolimus (MK-8669) + Dalotuzumab (MK-0646)

Drug: Ridaforolimus + Dalotuzumab

Ridaforolimus (MK-8669) once daily for 5 consecutive days per week and Dalotuzumab (MK-0646) intravenously (IV) once weekly for 2 weeks

Other Names:

MK-8669, MK-0646

Experimental: Ridaforolimus

Ridaforolimus (MK-8669)

Drug: Ridaforolimus

Ridaforolimus 40 mg (once daily for 5 consecutive days per week) for 2 weeks, 10 mg enteric-coated tablets

Other Names:

MK-8669

Experimental: Dalotuzumab

Dalotuzumab (MK-0646)

Drug: Dalotuzumab

Dalotuzumab, intravenously (IV) at 10 mg/kg/week for 2 weeks

Other Names:

MK-0646

Outcome Measures

Primary Outcome Measures

The population mean change from baseline in GFS (Growth Factor Signature) score [Baseline and Day 15]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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