A Study of Ridaforolimus (MK-8669) in Combination With Dalotuzumab (MK-0646) Compared to Standard of Care Treatment in Estrogen Receptor Positive Breast Cancer Patients (MK-8669-041 AM3)

Merck Sharp & Dohme (MSD)

Status and phase

Completed

Phase 2

Conditions

Breast Cancer

Treatments

Drug: ridaforolimus

Drug: ridaforolimus + dalotuzumab

Drug: exemestane

Drug: dalotuzumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT01234857

8669-041

Details and patient eligibility

About

This is a two-part study that will determine, if: 1) the combination of ridaforolimus and dalotuzumab will improve progression-free survival compared to exemestane; and 2) the combination of ridaforolimus and dalotuzumab will improve progression-free survival compared to both ridaforolimus and dalotuzumab as single agents, in participants with breast cancer.

Enrollment

115 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria The prospective participant must meet, at least, all of the criteria below to be eligible for study participation.

The participant:

Has a confirmed diagnosis of breast cancer that is metastatic or locally advanced and is estrogen receptor positive and human epidermal growth factor receptor 2 (HER-2) negative ;
Is post-menopausal;
Is at least 18 years of age;
Has a life expectancy of at least 3 months;
Has had a recurrence or progression of cancer after prior treatment and patient has received at least one line of endocrine therapy for metastatic disease, OR the patient's cancer has recurred within 6 months after the last dose of anastrozole or letrozole;
Has an available archival tumor specimen;
Has voluntarily agreed to participate by signing informed consent.

Exclusion Criteria If the prospective participant meets any of the criteria below (among others determined by the study staff) they will NOT be eligible for study participation.

The participant:

Is receiving any other systemic tumor therapy;
Has previously received rapamycin or rapamycin analogs;
Has received prior treatment with insulin-like growth factor 1 receptor (IGF-1R) inhibitors, phosphoinositide 3-kinase (PI3K) inhibitors, or other experimental agents that target the PI3K, protein kinase B (AKT), or mammalian target of rapamycin (mTOR) pathways;
Has known allergy to macrolide antibiotics;
Has an active infection that requires antibiotics;
Has significant or uncontrolled cardiovascular disease;
Has poorly controlled Type 1 or 2 diabetes mellitus;
Is known to be human immunodeficiency virus (HIV) positive;
Has a known history of active Hepatitis B or C.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

115 participants in 5 patient groups

Part A: ridaforolimus + dalotuzumab

Experimental group

Description:

Approximately 15 patients will be enrolled to the ridaforolimus-dalotuzumab combination treatment arm. Subsequent Patients are randomly assigned in a 1:1 ratio to treatment with the ridaforolimus (20 mg daily five days a week)/dalotuzumab (intravenous infusion 10 mg/kg once weekly) combination therapy or cross-over to exemestane single-therapy treatment.

Treatment:

Drug: ridaforolimus + dalotuzumab

Part A: exemestane

Active Comparator group

Description:

Exemestane 25 mg daily; single-agent therapy.

Treatment:

Drug: exemestane

Part B: ridaforolimus + dalotuzumab

Experimental group

Description:

Patients are randomly assigned in a 1:1 ratio to treatment with the ridaforolimus (20 mg daily five days a week)/dalotuzumab (intravenous infusion 10 mg/kg once weekly) combination therapy or cross-over to one of two single-therapy treatments (ridaforolimus alone or dalotuzumab alone). With the implementation of Amendment 3, this study arm will not be opened.

Treatment:

Drug: ridaforolimus + dalotuzumab

Part B: ridaforolimus

Experimental group

Description:

Ridaforolimus; 40 mg daily five days a week, single-agent therapy. With the implementation of Amendment 3, this study arm will not be opened.

Treatment:

Drug: ridaforolimus

Part B: dalotuzumab

Experimental group

Description:

Dalotuzumab intravenous infusion 10 mg/kg weekly; single-agent therapy. With the implementation of Amendment 3, this study arm will not be opened.