Vorinostat in Treating Patients With Stage IV Breast Cancer Receiving Aromatase Inhibitor Therapy
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01153672|
Recruitment Status : Completed
First Posted : June 30, 2010
Results First Posted : November 7, 2014
Last Update Posted : May 15, 2018
|Condition or disease||Intervention/treatment||Phase|
|Male Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer||Drug: vorinostat Other: laboratory biomarker analysis Procedure: biopsy Radiation: F-18 16 alpha-fluoroestradiol Procedure: positron emission tomography Drug: anastrozole Drug: letrozole Drug: exemestane Genetic: gene expression analysis||Not Applicable|
I. Determine the rate of clinical benefit (objective response plus stable disease) for patients treated with cycles consisting of 2 weeks of vorinostat followed by 6 weeks of AI therapy.
I. Assess the safety and tolerability of vorinostat in patients with metastatic breast cancer.
II. Assess the change in estrogen receptor (ER) expression, measured as the change in fluoroestradiol standard uptake value (FES SUV) using fluoroestradiol-positron emission tomography (FES-PET) completed per protocol 7184 after two weeks of vorinostat therapy and after 8 weeks of therapy.
III. Assess tumor metabolic response, measured as the change in fluorodeoxyglucose (FDG) SUV using FDG PET completed per protocol 7184 after two weeks of vorinostat therapy and after 8 weeks of therapy.
IV. Assess the change in hormone levels (estradiol, estrone, follicle-stimulating hormone [FSH], sex binding globulin, testosterone, and free testosterone) after 8 weeks of therapy.
V. Assess the change in ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), epithelial growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) tumor expression after two weeks of vorinostat therapy in patients that consent to optional tissue biopsy procedure.
VI. Assess the time to progression and the overall survival of patients treated with cycles of 2 weeks of vorinostat followed by 6 weeks of AI.
Patients receive vorinostat orally (PO) once daily (QD) for 2 weeks followed by AI therapy comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months until disease progression, and then annually thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Vorinostat to Restore Sensitivity to Aromatase Inhibitor Therapy|
|Study Start Date :||November 2010|
|Actual Primary Completion Date :||July 2012|
|Actual Study Completion Date :||August 11, 2016|
Experimental: Treatment (enzyme inhibitor therapy, AI sensitization therapy)
Patients receive vorinostat PO QD for 2 weeks followed by AI therapy comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
Other Names:Other: laboratory biomarker analysis
Correlative studiesProcedure: biopsy
Optional correlative studies
Other Name: biopsiesRadiation: F-18 16 alpha-fluoroestradiol
Other Names:Procedure: positron emission tomography
Other Names:Drug: anastrozole
Other Names:Drug: letrozole
Other Names:Drug: exemestane
Other Names:Genetic: gene expression analysis
- Rate of Clinical Benefit According to RECIST [ Time Frame: Up to approximately 5 years ]
A 90% score (Wilson) confidence interval will be computed for the response rate and the rate of clinical benefit. The radiological (by computed tomography [CT]) response rate of vorinostat will be determined by tumor measurements assessed by modified RECIST criteria.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) assessed by CT, Clinical Benefit was defined as an objective response (complete response [CR], partial response [PR]) or stable disease [SD]). CR=the disappearance of all target lesions; PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions; SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started; PD=at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum of the LD recorded since the treatment started or the appearance of 1 or more new lesions.
- Duration of Response [ Time Frame: Up to approximately 5 years ]Duration of response will be summarized for responders.
- Progression-free Survival [ Time Frame: Time elapsed from the first day of study treatment, until disease progression or death, assessed up to approximately 5 years ]Kaplan-Meier survival curves will be used to describe progression-free survival. For progression-free survival, patients without documented disease progression or death will be treated as censored observations on the date of the last tumor assessment.
- Overall Survival [ Time Frame: Time elapsed from the first day of study treatment until death, assessed up to approximately 5 years ]Kaplan-Meier survival curves will be used to describe overall survival. Overall survival time will be censored on the last date the patient was known to be alive.
- Percentage of Patients That Experience Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [ Time Frame: Up to approximately 5 years ]
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): NCT01153672
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Hannah Linden||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|