Pharmacokinetically Guided Everolimus in Patients With Breast Cancer, Pancreatic Neuroendocrine Tumors, or Kidney Cancer
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|ClinicalTrials.gov Identifier: NCT02273752|
Recruitment Status : Terminated (Slow accrual)
First Posted : October 24, 2014
Results First Posted : February 3, 2017
Last Update Posted : February 3, 2017
|Condition or disease||Intervention/treatment||Phase|
|Estrogen Receptor-positive Breast Cancer Gastrinoma Glucagonoma HER2-negative Breast Cancer Insulinoma Mucositis Oral Complications Pancreatic Polypeptide Tumor Progesterone Receptor-positive Breast Cancer Recurrent Breast Cancer Recurrent Islet Cell Carcinoma Recurrent Renal Cell Cancer Somatostatinoma Stage III Renal Cell Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer Stage IV Renal Cell Cancer||Drug: Everolimus||Phase 2|
To determine frequency of any grade of stomatitis at day 29 (cycle 2, day 1) in patients receiving dose-adjusted everolimus.
- Progression-free survival rates at 6 months.
- Pharmacodynamic (PD)-inhibition of downstream mammalian target of rapamycin (mTOR) effectors in peripheral blood.
- Number of dose adjustments required.
- Percentage of days on therapy.
- Average minimum concentration (Cmin) values.
- Frequency and type of treatments for stomatitis.
- Genetic predictors of stomatitis development in selected outlier patients.
Patients receive everolimus orally (PO) daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo real-time pharmacokinetic therapeutic drug monitoring (TDM) on days 4, 8, and 15 of course 1. Dosing adjustments of everolimus will be performed on day 8, if necessary. If the everolimus dose is adjusted, patients will continue to undergo real-time pharmacokinetic TDM weekly until goal concentrations are achieved on 2 consecutive measures. Patients whose everolimus dose is not adjusted undergo real-time pharmacokinetic TDM on day 1 of courses 2-6.
After completion of study treatment, patients are followed up every 12 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Evaluation of Real-Time, Pharmacokinetically Guided Everolimus in Patients With Hormone Receptor Positive Breast Cancer, Pancreatic Neuroendocrine Tumors (PNET), and Renal Cell Carcinoma|
|Study Start Date :||November 2014|
|Actual Primary Completion Date :||December 2015|
|Actual Study Completion Date :||December 2015|
Experimental: Supportive care (real-time pharmacokinetic TDM of everolimus)
Patients receive everolimus PO daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo real-time pharmacokinetic TDM on days 4, 8, and 15 of course 1. Dosing adjustments of everolimus will be performed on day 8, if necessary. If the everolimus dose is adjusted, patients will continue to undergo real-time pharmacokinetic TDM weekly until goal concentrations are achieved on 2 consecutive measures. Patients whose everolimus dose is not adjusted undergo real-time pharmacokinetic TDM on day 1 of courses 2-6.
- Incidence of Stomatitis [ Time Frame: Day 29 ]Stomatitis graded rates and severity will be evaluated and recorded per World Health Organization and Common Terminology Criteria for Adverse Events criteria in the study population.
- Progression Free Survival (PFS) [ Time Frame: 6 months ]PFS will be evaluated based on rates of cancer progression and time to progression in the population. Progression will be determined using standard RECIST criteria. The median PFS for this study will be estimated by Kaplan-Meier method along with 95% confidence interval.
- Downstream Markers of Mammalian Target of Rapamycin (mTOR) Function Measured in Peripheral Blood Mononuclear Cells [ Time Frame: Up to day 15 of course 1 ]Pharmacodynamics will be evaluated for phosphorylated and non-phosphorylated ribosomal protein S6 kinase, protein kinase B, and eukaryotic translation initiation factor 4E-binding protein 1.
- Percentage of Days on Therapy [ Time Frame: Up to 6 months ]Percentage of days on therapy will be calculated using the formula: (expected - actual days)/expected x 100.
- Dose Interruptions and Adjustments [ Time Frame: Up to 6 months ]Dose interruptions and adjustments will be made on a per subject basis and total for the population.
- Frequency of Treatments for Stomatitis [ Time Frame: Up to 6 months ]Frequency of treatments for stomatitis will be collection of prescription and non-prescription interventions.
- Type of Treatments for Stomatitis [ Time Frame: Up to 6 months ]Type of treatments for stomatitis will be collection of prescription and non-prescription interventions.
- Response Rate Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria [ Time Frame: Up to 24 weeks ]Response rate will be measured at different time points, e.g. 8, 16, and 24 weeks, and will be summarized as percentage of stable disease, complete remission or partial remission along with 95% confidence interval.
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): NCT02273752
|United States, Georgia|
|Emory University Hospital Midtown|
|Atlanta, Georgia, United States, 30308|
|Emory University/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|Principal Investigator:||R. Donald Harvey, PharmD||Emory University/Winship Cancer Institute|