Breast Cancer
Conditions
Keywords
mTOR, breast cancer, estrogen receptor positive
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.
Interventions
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.
DRUGexemestane
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.
DRUGridaforolimus
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.
DRUGdalotuzumab
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.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Outcome results
None listed