Clinical trial NCT02273752
Conditions: 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
Sponsor: Emory University
Start date: 2014-11-01; Completion date: 2015-12-01
Enrollment: 2 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II trial studies how well real-time pharmacokinetic therapeutic drug monitoring works in preventing stomatitis from developing in patients with hormone receptor positive breast cancer, pancreatic neuroendocrine tumors, or kidney cancer that are receiving a type of cancer drug called everolimus. Stomatitis is a common side effect of everolimus that causes inflammation of the mouth, with or without oral ulcers, and frequently leads to patients discontinuing the medication. Monitoring the blood levels of everolimus and making adjustments in a patient's dose may be able to decrease the incidence of stomatitis, while maintaining the effectiveness of everolimus to treat the cancer.

Detailed description:
PRIMARY OBJECTIVE:

To determine frequency of any grade of stomatitis at day 29 (cycle 2, day 1) in patients receiving dose-adjusted everolimus.

SECONDARY OBJECTIVES:

1. Progression-free survival rates at 6 months.
2. Pharmacodynamic (PD)-inhibition of downstream mammalian target of rapamycin (mTOR) effectors in peripheral blood.
3. Number of dose adjustments required.
4. Percentage of days on therapy.
5. Average minimum concentration (Cmin) values.
6. Frequency and type of treatments for stomatitis.
7. Genetic predictors of stomatitis development in selected outlier patients.

OUTLINE:

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.

Arms: arm 1: 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.
Interventions: intervention 1: Everolimus
Intervention descriptions: intervention 1: Given PO

Protocol documents: