ER positive, high proliferation breast MedDRA version: 14.1 Level: LLT Classification code 10070575 Term: Estrogen receptor positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Metastatic, ER positive, HER2 negative Breast Cancer 2. High Proliferative (as measured by a Ki67 labeling index >15%) 3. Post menopausal 4. Previous treatment with either letrozole or anastrozole 5. AT least 1 measurable lesion 6. At least 18 years of age 7. Greater than or equal to 1 on the ECOG performance status. 8. Life expectance greater than 3 months Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 75
Exclusion criteria
Exclusion criteria: 1. Patient is on other therapy for their cancer (Bisphosphonates and denosumab for the treatment of bone metastases are allowed, if they were initiated at least 28 days prior to randomization.) 2. Patient is in another study or is receiving an experimental agent. 3. Patient has previously received rapamycin or rapamycin analogs, including ridaforolimus, temsirolimus, or everolimus. 4. Patient has received prior treatment with IGF-1R inhibitors, PI3K inhibitors, or other experimental agents that target PI3K, AKT, or mTOR pathway 5. Patient who has had chemotherapy, radiotherapy, or biological therapy within 4 weeks [(6 weeks for nitrosoureas, mitomycin C, or bevacizumab and 2 weeks for hormonal therapy and kinase inhibitors)] prior to entering the study or who has not recovered from adverse events from prior treatment to at least grade 1 or baseline. 6. Patient has active brain metastasis or leptomeningeal carcinomatosis; 7. Patient has poorly controlled Type 1 or 2 diabetes, defined as a hemoglobin A1C greater than 8% or a fasting glucose of > 160 mg/dL. 8. Patient is known to be HIV positive. 9. Patient has a known history of active Hepatitis B or C. Patients who are seropositive for Hepatitis B surface antibody as their only evidence of prior hepatitis exposure are allowed. 10. Patient has a requirement for concurrent treatment with medications that are inducers or inhibitors of cytochrome P450 (CYP3A). Patients should be off these medications for at least 2 weeks prior to the first dose of ridaforolimus. Concomitant medications that are metabolized by CYP3A are allowed (e.g., simvastatin or atorvastatin). See Appendix 6.1 for examples of CYP3A inducers and inhibitors.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 1.Progression Free Survival according to RECIST 1.1.;Timepoint(s) of evaluation of this end point: Every 8 calendar weeks while on treatment;Main Objective: The primary objective of the study is to evaluate the progression free survival (PFS) for the triplet combination of ridaforolimus, dalotuzumab and exemestane (R/D/E) compared to the combination of ridaforolimus and exemestane (R/E) in post-menopausal patients with high proliferation, estrogen receptor positive breast cancer that have progressed following treatment with a non-steroidal aromatase inhibitor.;Secondary Objective: ? In post-menopausal patients with high proliferation, estrogen receptor positive breast cancer who have progressed following treatment with a non-steroidal aromatase inhibitor, the secondary objectives of this trial are the following: ?To evaluate the effectiveness of the triplet combination of ridaforolimus, exemestane and dalotuzumab (R/D/E) compared to ridaforolimus and exemestane (R/E) with respect to percent (%) reduction from baseline in the sum of imaging measurements (target lesion line lengths or volumetric images) at 16 weeks. ?To evaluate the objective response rate, as measured by RECIST 1.1 of the triplet combination of R/D/E compared to the combination of R/E. ?To estimate the overall survival for the triplet combination of R/D/E compared to the combination of R/E. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percent (%) change from baseline in the sum of target lesions by linear CT analysis at 16 weeks. 2. Percent (%) change from baseline in the sum of target lesions by tumor volume analysis at 16 weeks 3. Objective response rate, as measured by RECIST 1.1. 4. Overall survival will be assessed every 3 months;Timepoint(s) of evaluation of this end point: :16 weeks for endpoints 1 and 2. Every 8 weeks for objective 3 every three months after disease progression. | — |
Countries
Belgium, Brazil, Canada, Colombia, Czech Republic, Denmark, Germany, Israel, Italy, Korea, Democratic People's Republic of, Peru, Portugal, Spain, Sweden, Taiwan, United States
Contacts
Public ContactMarta Arias-Salgado
Merck, Sharp & Dohme de España, S.A.
Outcome results
None listed