A Pharmacodynamic Study of Sirolimus in Older Children and Adults With Advanced Solid Malignancies
12 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific, Unspecified Childhood Solid Tumor, Protocol Specific
Trial Information
A Pharmacodynamic Study of Sirolimus in Older Children and Adults With Advanced Solid Malignancies
PRIMARY OBJECTIVES:
I. To describe the magnitude, inter-individual variability and time course of
sirolimus-induced changes in fasting serum glucose and triglycerides.
SECONDARY OBJECTIVES:
I. To assess candidate genetic variants for their correlation with changes in fasting
glucose and/or triglycerides.
II. To assess tumor response by the Response Evaluation Criteria In Solid Tumors (RECIST,
version 1.1) and explore whether there is any correlation between response and changes in
fasting glucose and/or triglycerides.
III. To assess toxicity by the Common Terminology Criteria for Adverse Events (CTCAE,
version 4.0) and explore whether there is any correlation between toxicities and changes in
fasting glucose and/or triglycerides.
IV. To quantify and determine the functional status of circulating regulatory T cells
(Tregs) before and during treatment.
OUTLINE:
Patients receive sirolimus orally (PO) on days 1-28. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.
Inclusion Criteria:
- Histologically or cytologically confirmed solid tumor that is metastatic or
unresectable and for which standard curative or palliative measures do not exist or
are no longer effective
- Weight >= 40 kg
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- Life expectancy > 3 months
- Absolute neutrophil count (ANC) >= l500/ul
- Hemoglobin >= 9g/dL
- Platelets >= 100,000/ ul
- Total bilirubin < 1.5 x upper limit of normal
- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate
transaminase (SGPT) < 2.5 x upper limit of normal for patients without liver
metastases OR SGOT and SGPT < 5 x upper limit of normal for patients with liver
metastases
- Measurable or non-measurable disease will be allowed
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation, up until 30 days after final study
treatment; should a woman become pregnant or suspect that she is pregnant while
participating in this study, she should inform her treating physician immediately
- Patients taking substrates, inhibitors, or inducers of cytochrome P450 (CYP)3A4
should be encouraged to switch to alternative drugs whenever possible, given the
potential for drug-drug interactions with sirolimus
- Signed informed consent
Exclusion Criteria:
- Prior treatment with a mammalian target of rapamycin (mTOR) inhibitor (including
sirolimus) is allowed; however, patients with >= grade 3 toxicities with an mTOR
inhibitor are excluded
- Fasting glucose > 126 mg/dL or fasting triglycerides > 150 mg/dL; patients are
allowed to be on oral anti-hyperglycemic and anti-lipid therapies, but cannot be on
insulin
- Patients who have had chemotherapy or immunotherapy within 3 weeks of starting study
drug, or radiotherapy within 14 days of starting study drug, or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents or any concomitant
antineoplastic therapy, with the exception of androgen ablating agents (for patients
with prior prostate cancer)
- Serious underlying medical or psychiatric illnesses that would, in the opinion of the
treating physician, substantially increase the risk for complications related to
treatment; similarly, any unstable medical condition that in the opinion of the
treating physician or study investigators, would interfere with determination of the
study objectives
- Pregnancy or breastfeeding
- Major surgery within 4 weeks
Type of Study:
Interventional
Study Design:
Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Change in fasting glucose and fasting triglycerides
Outcome Description:
These data will be analyzed by fitting mixed effects models for longitudinal data. A model linear in time with random patient intercept and slope effects will be fit initially and residuals examined. If a linear model does not fit the data adequately a quadratic term will be added. Simple paired t-tests of the glucose and triglyceride levels on day 8, 15, and 29 relative to baseline will also be performed.
Outcome Time Frame:
Baseline to 8 days
Safety Issue:
No
Principal Investigator
Manish R Sharma, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Chicago Comprehensive Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
12-1169
NCT ID:
NCT01791088
Start Date:
June 2012
Completion Date:
July 2015
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- Unspecified Childhood Solid Tumor, Protocol Specific
- Neoplasms
Name | Location |
|---|---|
| University of Chicago Comprehensive Cancer Center | Chicago, Illinois 60637-1470 |
