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)

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01234857
• Other study ID #: 8669-041
• Status: Completed
• Phase: Phase 2
• First received: September 22, 2010
• Last updated: May 29, 2017
• Start date: September 17, 2010
• Est. completion date: October 15, 2013

Study information

• Verified date: May 2017
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 115
• Est. completion date: October 15, 2013
• Est. primary completion date: October 15, 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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 dalotuz — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (PFS)	Progression free survival is defined as the time from randomization to progressive disease or death, which ever occurs earlier.	Assessed every 8 weeks until documentation of disease progression or death.
Secondary	Objective response rate (ORR)	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	Assessed every 8 weeks until documentation of disease progression or death.
Secondary	Overall survival (OS)	Overall survival is defined as the time from randomization to death due to any cause.	Every 3 months after participants go off active treatment