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
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: ridaforolimus + dalotuzumab
Drug: exemestane
Drug: ridaforolimus
Drug: dalotuzumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 115
Study Start Date: September 2010
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
Active Comparator: Part A: exemestane
Exemestane 25 mg daily; single-agent therapy.
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.
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.
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
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.
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
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.
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01234857     History of Changes
Other Study ID Numbers: 8669-041
Study First Received: September 22, 2010
Last Updated: November 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
mTOR
breast cancer
estrogen receptor positive

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Estrogens
Exemestane
Sirolimus
Antibodies, Monoclonal
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antibiotics, Antineoplastic
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 26, 2014