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)

NCT ID: NCT01234857

Last Updated: 2017-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-17
• Study Completion Date: 2013-10-15

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

ridaforolimus + dalotuzumab

Intervention Type: 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.

Part A: exemestane

Exemestane 25 mg daily; single-agent therapy.

Group Type: ACTIVE_COMPARATOR

exemestane

Intervention Type: 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 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.

Group Type: EXPERIMENTAL

ridaforolimus + dalotuzumab

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

ridaforolimus

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

dalotuzumab

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

MK-8669, MK-0646; MK-8669; MK-0646

Eligibility Criteria

Inclusion Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

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.

Reference Type: RESULT

PMID: 28324268 (View on PubMed)

Other Identifiers

8669-041

Identifier Type: -

Identifier Source: org_study_id