Clinical trial NCT01605396: A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064)
Official title: A Phase II Randomized Trial of the Combination of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in High Proliferation, Estrogen Receptor Positive Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Neoplasms
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-05-24
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 1. Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)
timeFrame: From Day 1 through last post-study efficacy follow-up (up to ~19 months)
Secondary outcomes:
measure: Percent Change From Baseline in Sum of Target Lesion Diameters at Week 16
timeFrame: Baseline, Week 16
measure: 3. Percentage of Participants With Objective Response (Objective Response Rate [ORR]) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR).
timeFrame: From Day 1 through last post-study efficacy follow-up (up to ~19 months)
measure: Overall Survival (OS)
timeFrame: From Day 1 through last post-study efficacy follow-up (up to ~19 months)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.