Clinical trial NCT01234857: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: mTOR
breast cancer
estrogen receptor positive
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-11-04
Enrollment: 115
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: Assessed every 8 weeks until documentation of disease progression or death.
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Assessed every 8 weeks until documentation of disease progression or death.
measure: Overall survival (OS)
timeFrame: Every 3 months after participants go off active treatment
Other outcomes:
Locations:
Study officials:
References:
citation: Baselga J, Morales SM, Awada A, Blum JL, Tan AR, Ewertz M, Cortes J, Moy B, Ruddy KJ, Haddad T, Ciruelos EM, Vuylsteke P, Ebbinghaus S, Im E, Eaton L, Pathiraja K, Gause C, Mauro D, Jones MB, Rugo HS. A phase II study of combined ridaforolimus and dalotuzumab compared with exemestane in patients with estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2017 Jun;163(3):535-544. doi: 10.1007/s10549-017-4199-3. Epub 2017 Mar 21.