Overview

This trial is active, not recruiting.

Conditions unspecified adult solid tumor, protocol specific, unspecified childhood solid tumor, protocol specific
Treatments sirolimus, pharmacological study, laboratory biomarker analysis
Target mTOR
Sponsor University of Chicago
Collaborator National Cancer Institute (NCI)
Start date June 2012
End date June 2017
Trial size 50 participants
Trial identifier NCT01791088, 12-1169, NCI-2012-01166

Summary

This clinical trial studies sirolimus in treating patients with solid tumors that are metastatic or cannot be removed by surgery. Sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification pharmacodynamics study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive sirolimus PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
sirolimus AY 22989
Given PO
pharmacological study pharmacological studies
Correlative studies
laboratory biomarker analysis
Correlative studies

Primary Outcomes

Measure
Change in fasting glucose and fasting triglycerides
time frame: Baseline to 8 days
Change in fasting glucose and fasting triglycerides
time frame: Baseline to 15 days
Change in fasting glucose and fasting triglycerides
time frame: Baseline to 29 days

Secondary Outcomes

Measure
Association between genetic variants and changes in fasting glucose and triglycerides
time frame: Up to 12 months
Change in tumor size assessed using RECIST
time frame: Up to 2 years
Correlation of toxicities graded using CTCAE version 4.0 with glucose/triglyceride changes
time frame: Up to 2 years
Regulatory T cells (Tregs)
time frame: Baseline to 28 days

Eligibility Criteria

Male or female participants at least 12 years old.

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

Additional Information

Official title A Pharmacodynamic Study of Sirolimus in Older Children and Adults With Advanced Solid Malignancies
Principal investigator Manish R Sharma, MD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by University of Chicago.