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)

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT01234857

Collaborator

(none)

115

Enrollment

Arms

36.9

Actual Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: ridaforolimus + dalotuzumab Drug: exemestane Drug: ridaforolimus Drug: dalotuzumab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

115 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Two-Part Adaptive, Randomized Trial of Ridaforolimus in Combination With Dalotuzumab Compared to Exemestane or Compared to Ridaforolimus or Dalotuzumab Monotherapy in Estrogen Receptor Positive Breast Cancer Patients

Actual Study Start Date :

Sep 17, 2010

Actual Primary Completion Date :

Oct 15, 2013

Actual Study Completion Date :

Oct 15, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: ridaforolimus + dalotuzumab 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.	Drug: ridaforolimus + dalotuzumab Ridaforolimus 20 mg once daily (QD) five days a week, with the possibility of escalation to 30 mg once daily (QD) after the first cycle and dalotuzumab intravenous infusion 10 mg/kg once weekly (QW). Treatment will continue until disease progression. Other Names: MK-8669, MK-0646
Active Comparator: Part A: exemestane Exemestane 25 mg daily; single-agent therapy.	Drug: exemestane Exemestane 25 mg daily (QD). Treatment will continue until disease progression. Patients may cross-over to the combination therapy after disease progression at the discretion of the investigator with Sponsor approval.
Experimental: Part B: ridaforolimus + dalotuzumab 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.	Drug: ridaforolimus + dalotuzumab Ridaforolimus 20 mg once daily (QD) five days a week, with the possibility of escalation to 30 mg once daily (QD) after the first cycle and dalotuzumab intravenous infusion 10 mg/kg once weekly (QW). Treatment will continue until disease progression. Other Names: MK-8669, MK-0646
Experimental: Part B: ridaforolimus Ridaforolimus; 40 mg daily five days a week, single-agent therapy. With the implementation of Amendment 3, this study arm will not be opened.	Drug: ridaforolimus Ridaforolimus 40 mg QD five days a week. Treatment will continue until disease progression. Patients may cross-over to the combination therapy after disease progression at the discretion of the investigator with Sponsor approval. Note: the Sponsor-recommended dose of ridaforolimus when administered as a single agent is 40 mg/day, but when given in combination with dalotuzumab, it is given at 30 mg/day. Other Names: MK-8669
Experimental: Part B: dalotuzumab Dalotuzumab intravenous infusion 10 mg/kg weekly; single-agent therapy. With the implementation of Amendment 3, this study arm will not be opened.	Drug: dalotuzumab Dalotuzumab intravenous infusion 10 mg/kg QW. Treatment will continue until disease progression. Patients may cross-over to the combination therapy after disease progression at the discretion of the investigator with Sponsor approval. Other Names: MK-0646

Outcome Measures

Primary Outcome Measures

Progression free survival (PFS) [Assessed every 8 weeks until documentation of disease progression or death.]
Progression free survival is defined as the time from randomization to progressive disease or death, which ever occurs earlier.

Secondary Outcome Measures

Objective response rate (ORR) [Assessed every 8 weeks until documentation of disease progression or death.]
Objective response rate (ORR) will be estimated by the proportion of patients who achieve partial response (PR) or complete response (CR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Overall survival (OS) [Every 3 months after participants go off active treatment]
Overall survival is defined as the time from randomization to death due to any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.