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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01234857
First received: September 22, 2010
Last updated: November 5, 2013
Last verified: November 2013

September 22, 2010
November 5, 2013
September 2010
October 2013   (final data collection date for primary outcome measure)
Progression free survival (PFS) [ Time Frame: Assessed every 8 weeks until documentation of disease progression or death. ] [ Designated as safety issue: No ]
Progression free survival is defined as the time from randomization to progressive disease or death, which ever occurs earlier.
Same as current
Complete list of historical versions of study NCT01234857 on ClinicalTrials.gov Archive Site
  • Objective response rate (ORR) [ Time Frame: Assessed every 8 weeks until documentation of disease progression or death. ] [ Designated as safety issue: No ]
    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) [ Time Frame: Every 3 months after participants go off active treatment ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from randomization to death due to any cause.
Same as current
Not Provided
Not Provided
 
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)
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
  • 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 Name: MK-8669, MK-0646
  • 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.
  • 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 Name: MK-8669
  • 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 Name: MK-0646
  • 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.
    Intervention: Drug: ridaforolimus + dalotuzumab
  • Active Comparator: Part A: exemestane
    Exemestane 25 mg daily; single-agent therapy.
    Intervention: Drug: exemestane
  • 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.
    Intervention: Drug: ridaforolimus + dalotuzumab
  • 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.
    Intervention: Drug: ridaforolimus
  • 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.
    Intervention: Drug: dalotuzumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
115
October 2013
October 2013   (final data collection date for primary outcome measure)

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.
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01234857
8669-041
Yes
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP