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)

NCT01234857 | Completed Phase 2 DMC

• 1 other identifier: 8669-041
• Study Type: interventional
• Target: 115
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Breast Cancer

Keywords

mTOR; breast cancer; estrogen receptor positive

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Objective response rate (ORR)

  Assessed every 8 weeks until documentation of disease progression or death.

• Overall survival (OS)

  Every 3 months after participants go off active treatment

Study Arms (5)

Part A: ridaforolimus + dalotuzumab

EXPERIMENTAL

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

Part A: exemestane

ACTIVE COMPARATOR

Exemestane 25 mg daily; single-agent therapy.

Drug: exemestane

Part B: ridaforolimus + dalotuzumab

EXPERIMENTAL

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

Part B: ridaforolimus

EXPERIMENTAL

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

Part B: dalotuzumab

EXPERIMENTAL

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

Interventions

ridaforolimus + dalotuzumab DRUG

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.

Also known as: MK-8669, MK-0646

Part A: ridaforolimus + dalotuzumab; Part B: ridaforolimus + dalotuzumab

exemestane DRUG

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.

Part A: exemestane

ridaforolimus DRUG

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.

Also known as: MK-8669

Part B: ridaforolimus

dalotuzumab DRUG

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.

Also known as: MK-0646

Part B: dalotuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related 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 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.

  PMID: 28324268 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ridaforolimus; dalotuzumab; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2010
• First Posted: November 4, 2010
• Study Start: September 17, 2010
• Primary Completion: October 15, 2013
• Study Completion: October 15, 2013
• Last Updated: May 31, 2017

Record last verified: 2017-05