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A Pharmacodynamic Study of Sirolimus in Older Children and Adults With Advanced Solid Malignancies


N/A
12 Years
N/A
Open (Enrolling)
Both
Unspecified Adult Solid Tumor, Protocol Specific, Unspecified Childhood Solid Tumor, Protocol Specific

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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 CenterChicago, Illinois  60637-1470