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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
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
R. Donald Harvey, PharmD, Emory University

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
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
Intervention Drug: Everolimus
Enrollment 2
Recruitment Details Patient were recruited at Winship Cancer Institute of Emory University from November 2014 to December 2015.
Pre-assignment Details  
Arm/Group Title Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Hide Arm/Group Description

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 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.

Everolimus: Given PO

Period Title: Overall Study
Started 2
Completed 0
Not Completed 2
Reason Not Completed
Trial was terminated early             2
Arm/Group Title Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Hide Arm/Group Description

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.

Everolimus: Given PO

Overall Number of Baseline Participants 2
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
<=18 years
0
   0.0%
Between 18 and 65 years
1
  50.0%
>=65 years
1
  50.0%
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
Female
1
  50.0%
Male
1
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
2
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
2
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 2 participants
2
 100.0%
1.Primary Outcome
Title Incidence of Stomatitis
Hide Description 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.
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Trial was closed early due to lack of timely accrual. Because study was not fully enrolled, outcomes were unable to be measured accurately.
Arm/Group Title Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Hide Arm/Group Description:

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.

Everolimus: Given PO

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description 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.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Trial was closed early due to lack of timely accrual. Because study was not fully enrolled, outcomes were unable to be measured accurately.
Arm/Group Title Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Hide Arm/Group Description:

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.

Everolimus: Given PO

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Downstream Markers of Mammalian Target of Rapamycin (mTOR) Function Measured in Peripheral Blood Mononuclear Cells
Hide Description 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.
Time Frame Up to day 15 of course 1
Hide Outcome Measure Data
Hide Analysis Population Description
Trial was closed early due to lack of timely accrual. Because study was not fully enrolled, outcomes were unable to be measured accurately.
Arm/Group Title Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Hide Arm/Group Description:

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.

Everolimus: Given PO

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Percentage of Days on Therapy
Hide Description Percentage of days on therapy will be calculated using the formula: (expected - actual days)/expected x 100.
Time Frame Up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Trial was closed early due to lack of timely accrual. Because study was not fully enrolled, outcomes were unable to be measured accurately.
Arm/Group Title Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Hide Arm/Group Description:

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.

Everolimus: Given PO

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Dose Interruptions and Adjustments
Hide Description Dose interruptions and adjustments will be made on a per subject basis and total for the population.
Time Frame Up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Trial was closed early due to lack of timely accrual. Because study was not fully enrolled, outcomes were unable to be measured accurately.
Arm/Group Title Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Hide Arm/Group Description:

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.

Everolimus: Given PO

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Frequency of Treatments for Stomatitis
Hide Description Frequency of treatments for stomatitis will be collection of prescription and non-prescription interventions.
Time Frame Up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Trial was closed early due to lack of timely accrual. Because study was not fully enrolled, outcomes were unable to be measured accurately.
Arm/Group Title Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Hide Arm/Group Description:

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.

Everolimus: Given PO

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Type of Treatments for Stomatitis
Hide Description Type of treatments for stomatitis will be collection of prescription and non-prescription interventions.
Time Frame Up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Trial was closed early due to lack of timely accrual. Because study was not fully enrolled, outcomes were unable to be measured accurately.
Arm/Group Title Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Hide Arm/Group Description:

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.

Everolimus: Given PO

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Response Rate Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Hide Description 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.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Trial was closed early due to lack of timely accrual. Because study was not fully enrolled, outcomes were unable to be measured accurately.
Arm/Group Title Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Hide Arm/Group Description:

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.

Everolimus: Given PO

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Hide Arm/Group Description

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.

Everolimus: Given PO

All-Cause Mortality
Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Affected / at Risk (%)
Total   0/2 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Supportive Care (Real-time Pharmacokinetic TDM of Everolimus)
Affected / at Risk (%)
Total   2/2 (100.00%) 
Blood and lymphatic system disorders   
Thrombocytopenia *  1/2 (50.00%) 
Anemia *  1/2 (50.00%) 
Gastrointestinal disorders   
Mucositis *  1/2 (50.00%) 
General disorders   
Fatigue *  1/2 (50.00%) 
Metabolism and nutrition disorders   
Elevated glucose *  2/2 (100.00%) 
Hypertriglyceridemia *  1/2 (50.00%) 
Skin and subcutaneous tissue disorders   
Generalized acne *  1/2 (50.00%) 
*
Indicates events were collected by non-systematic assessment
Trial closed early due to lack of timely accrual.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: R. Donald Harvey, PharmD
Organization: Emory University
Phone: 404-778-1900
EMail: donald.harvey@emory.edu
Layout table for additonal information
Responsible Party: R. Donald Harvey, PharmD, Emory University
ClinicalTrials.gov Identifier: NCT02273752     History of Changes
Other Study ID Numbers: IRB00072091
NCI-2014-02112 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
WINSHIP2645-14 ( Other Identifier: Emory University/Winship Cancer Institute )
First Submitted: October 22, 2014
First Posted: October 24, 2014
Results First Submitted: December 9, 2016
Results First Posted: February 3, 2017
Last Update Posted: February 3, 2017