A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064)
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ClinicalTrials.gov Identifier: NCT01605396 |
Recruitment Status :
Completed
First Posted : May 24, 2012
Results First Posted : March 25, 2019
Last Update Posted : March 25, 2019
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Condition or disease | Intervention/treatment | Phase |
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Breast Neoplasms | Drug: Ridaforolimus Drug: Dalotuzumab Drug: Exemestane | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 80 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | July 4, 2012 |
Actual Primary Completion Date : | February 19, 2014 |
Actual Study Completion Date : | March 15, 2018 |
Arm | Intervention/treatment |
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Experimental: 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.
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Drug: 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.
Other Names:
Drug: Dalotuzumab Dalotuzumab administered 10 mg/kg IV weekly on Days 1, 8, 15, and 22 of 28-day cycle.
Other Names:
Drug: Exemestane Exemestane 25 mg tablet administered PO QD.
Other Name: Aromasin |
Active Comparator: 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.
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Drug: 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.
Other Names:
Drug: Exemestane Exemestane 25 mg tablet administered PO QD.
Other Name: Aromasin |
- 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) [ Time Frame: From Day 1 through last post-study efficacy follow-up (up to ~19 months) ]PFS was defined as the time from randomization to progressive disease, or death, whichever occurs first. Response was assessed according to RECIST 1.1 by BICR. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval [CI]) in weeks was reported for each treatment arm. Per protocol, participants remained on assigned treatment until disease progression. Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression. All participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.
- Percent Change From Baseline in Sum of Target Lesion Diameters at Week 16 [ Time Frame: Baseline, Week 16 ]The percent change from baseline to Week 16 in the sum of target lesion diameters as determined by anatomic imaging was defined as the line length (i.e., diameter) for each target lesion identified at baseline summed across all lesions at baseline, and separately at each post-baseline time point. The primary analysis was conducted using a constrained longitudinal data analysis (cLDA) method and target lesion measurements according to the BICR. Percent change from baseline in sum of target lesion diameters at Week 16 was reported for each treatment arm.
- 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). [ Time Frame: From Day 1 through last post-study efficacy follow-up (up to ~19 months) ]ORR was defined as the percentage of participants whose best response was complete response (CR; disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or partial response (PR; at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR. ORR was reported for each treatment arm. Per protocol, participants remained on assigned treatment until disease progression. Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression.
- Overall Survival (OS) [ Time Frame: From Day 1 through last post-study efficacy follow-up (up to ~19 months) ]OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date last known to be alive. OS was analyzed using the Kaplan-Meier method and median OS (95% confidence interval [CI]) in weeks was reported for each treatment arm. Per protocol, all participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01605396
Study Director: | Medical Director | Merck Sharp & Dohme LLC |
Responsible Party: | Merck Sharp & Dohme LLC |
ClinicalTrials.gov Identifier: | NCT01605396 |
Other Study ID Numbers: |
8669-064 2012-000335-11 ( EudraCT Number ) MK-8669-064 ( Other Identifier: Merck ) |
First Posted: | May 24, 2012 Key Record Dates |
Results First Posted: | March 25, 2019 |
Last Update Posted: | March 25, 2019 |
Last Verified: | March 2019 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
URL: | http://engagezone.msd.com/ds_documentation.php |
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Exemestane Antineoplastic Agents Aromatase Inhibitors |
Steroid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |