A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064)

NCT ID: NCT01605396

Last Updated: 2019-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-04
• Study Completion Date: 2018-03-15

Brief Summary

The purpose of the study is to evaluate the efficacy of the triplet of ridaforolimus, dalotuzumab and exemestane compared to the combination of ridaforolimus and exemestane in post-menopausal participants with breast cancer. The primary hypothesis of the study is that the triplet of ridaforolimus, dalotuzumab and exemestane will improve progression free survival (PFS) compared to ridaforolimus and exemestane.

Conditions

Breast Neoplasms

Study Design

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

Study Groups

Ridaforolimus + Dalotuzumab + Exemestane

Participants receive ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Ridaforolimus

Intervention Type: DRUG

Ridaforolimus 10 mg tablet, administered PO at a dose of 10 mg (triplet) or 30 mg (doublet) depending upon randomization, on Days 1-5, 8-12, 15-19, \& 22-26 of 28-day cycle.

Dalotuzumab

Intervention Type: DRUG

Dalotuzumab administered 10 mg/kg IV weekly on Days 1, 8, 15, and 22 of 28-day cycle.

Exemestane

Intervention Type: DRUG

Exemestane 25 mg tablet administered PO QD.

Ridaforolimus + Exemestane

Participants receive ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.

Group Type: ACTIVE_COMPARATOR

Ridaforolimus

Intervention Type: DRUG

Ridaforolimus 10 mg tablet, administered PO at a dose of 10 mg (triplet) or 30 mg (doublet) depending upon randomization, on Days 1-5, 8-12, 15-19, \& 22-26 of 28-day cycle.

Exemestane

Intervention Type: DRUG

Exemestane 25 mg tablet administered PO QD.

Interventions

Ridaforolimus

Ridaforolimus 10 mg tablet, administered PO at a dose of 10 mg (triplet) or 30 mg (doublet) depending upon randomization, on Days 1-5, 8-12, 15-19, \& 22-26 of 28-day cycle.

Intervention Type: DRUG

Dalotuzumab

Dalotuzumab administered 10 mg/kg IV weekly on Days 1, 8, 15, and 22 of 28-day cycle.

Intervention Type: DRUG

Exemestane

Exemestane 25 mg tablet administered PO QD.

Intervention Type: DRUG

Other Intervention Names

MK-8669; AP23573; MK-0646; h7C10; Aromasin

Eligibility Criteria

Inclusion Criteria

• Females with a histologically confirmed diagnosis of breast cancer that is metastatic or locally advanced (locally advanced tumors must not be amenable to

surgery or radiation therapy with curative intent) with the following pathological characteristics determined locally: estrogen receptor positive and Human Epidermal Growth Factor Receptor 2 (HER-2) negative, and Ki67 (a tumor marker) ≥ 15% determined by the central study laboratory

• Post-menopausal
• With advanced breast cancer whose disease was refractory to previous letrozole or anastrozole
• Has at least one confirmed measurable metastatic lesion
• Has a performance status ≤ 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Has a life expectancy of at least 3 months
• Adequate organ function

Exclusion Criteria

• Is receiving any other concurrent systemic tumor therapy, including

hormonal agents and HER-2 inhibitors

• Previously received rapamycin or rapamycin analogs, including

ridaforolimus, temsirolimus, or everolimus

• Received prior treatment with Insulin-like Growth Factor 1 Receptor (IGF-1R) inhibitors, Phosphatidylinositol 3-Kinase (PI3K) inhibitors, or

other experimental agents that target PI3K, Protein Kinase B (AKT), or Mammalian Target of Rapamycin (mTOR) pathway

• Is receiving chronic corticosteroids administered at doses greater than

those used for normal replacement therapy

• Has active brain metastasis or leptomeningeal carcinomatosis; patients

with adequately treated brain metastases are eligible if they meet certain criteria

• Known allergy to macrolide antibiotics
• Has an active infection requiring antibiotics
• Significant or uncontrolled cardiovascular disease
• Poorly controlled Type 1 or 2 diabetes
• Is known to be Human Immunodeficiency Virus (HIV) positive
• Has a known history of active hepatitis B or C. Healthy carriers of hepatitis B are not allowed on this study

• 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

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Rugo HS, Tredan O, Ro J, Morales SM, Campone M, Musolino A, Afonso N, Ferreira M, Park KH, Cortes J, Tan AR, Blum JL, Eaton L, Gause CK, Wang Z, Im E, Mauro DJ, Jones MB, Denker A, Baselga J. A randomized phase II trial of ridaforolimus, dalotuzumab, and exemestane compared with ridaforolimus and exemestane in patients with advanced breast cancer. Breast Cancer Res Treat. 2017 Oct;165(3):601-609. doi: 10.1007/s10549-017-4375-5. Epub 2017 Jul 5.

Reference Type: RESULT

PMID: 28681171 (View on PubMed)

Other Identifiers

2012-000335-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-8669-064

Identifier Type: OTHER

Identifier Source: secondary_id

8669-064

Identifier Type: -

Identifier Source: org_study_id