Sirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed By Surgery

NCT01791088 | Completed Phase 1

• 2 other identifiers: 12-1169NCI-2012-01166
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (3)

• Change in fasting glucose and fasting triglycerides

  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.

  Baseline to 8 days

• Change in fasting glucose and fasting triglycerides

  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.

  Baseline to 15 days

• Change in fasting glucose and fasting triglycerides

  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.

  Baseline to 29 days

Secondary Outcomes (4)

• Association between genetic variants and changes in fasting glucose and triglycerides

  Up to 12 months

• Change in tumor size assessed using RECIST

  Up to 2 years

• Correlation of toxicities graded using CTCAE version 4.0 with glucose/triglyceride changes

  Up to 2 years

• Regulatory T cells (Tregs)

  Baseline to 28 days

Study Arms (1)

Treatment (sirolimus)

EXPERIMENTAL

Patients receive sirolimus PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: sirolimus; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

sirolimus DRUG

Given PO

Also known as: AY 22989, Rapamune, rapamycin, SLM

Treatment (sirolimus)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (sirolimus)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (sirolimus)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Chicago: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637-1470, United States

Location

MeSH Terms

Interventions

Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Manish R Sharma, MD

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2013
• First Posted: February 13, 2013
• Study Start: June 13, 2012
• Primary Completion: August 17, 2018
• Study Completion: August 17, 2018
• Last Updated: April 22, 2019

Record last verified: 2019-04

Locations

US (1)