Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT01791088
Sirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed By Surgery
A Phase 1 study testing sirolimus, pharmacological study and laboratory biomarker analysis in people with Unspecified Adult Solid Tumor, Protocol Specific and Unspecified Childhood Solid Tumor, Protocol Specific, run by University of Chicago at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Unspecified Adult Solid Tumor, Protocol Specific, Unspecified Childhood Solid Tumor, Protocol Specific
- What is being tested?
- sirolimus, pharmacological study and laboratory biomarker analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jun 2012to 17 Aug 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637-1470
About this study
Official title: A Pharmacodynamic Study of Sirolimus in Older Children and Adults With Advanced Solid Malignancies
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
Read the detailed description
PRIMARY OBJECTIVES:
- To describe the magnitude, inter-individual variability and time course of sirolimus-induced changes in fasting serum glucose and triglycerides.
SECONDARY OBJECTIVES:
- 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.
- Conditions
- Unspecified Adult Solid Tumor, Protocol Specific, Unspecified Childhood Solid Tumor, Protocol Specific
- Being tested
- sirolimus, pharmacological study, laboratory biomarker analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimusDrug
Also called AY 22989, Rapamune, rapamycin, SLM
Given PO
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: sirolimus; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline to 29 days
Secondary outcomes (4)
Association between genetic variants and changes in fasting glucose and triglycerides
Two-sample t tests will be performed. A Bonferroni adjustment will be applied to control for the number of candidate markers evaluated. Logistic regression models will be fit to determine whether changes in glucose and/or triglycerides are associated with tumor response (complete or partial).
Measured: Up to 12 months
Change in tumor size assessed using RECIST
The change in tumor size will be plotted against the change in glucose/triglyceride and Pearson correlation coefficients will be calculated.
Measured: Up to 2 years
Correlation of toxicities graded using CTCAE version 4.0 with glucose/triglyceride changes
Proportional odds models will be fit to assess whether there is a correlation between toxicities (graded from 0 to 5) and glucose/triglyceride changes.
Measured: Up to 2 years
Regulatory T cells (Tregs)
Descriptive statistics will be used to report the quantity and phenotype of Tregs on days 1 and 29 of therapy.
Measured: Baseline to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2013 (estimated)
- Study start13 Jun 2012
- Primary completion17 Aug 2018
- Study completion17 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unspecified Adult Solid Tumor, Protocol SpecificStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Manish R Sharma, MD, Principal investigator, University of Chicago Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01791088
- Sponsor's protocol ID
- 12-1169
- Other IDs
- NCI-2012-01166
- Status last verified
- Apr 2019
- First submitted
- 11 Feb 2013
- Last updated
- 22 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacodynamic Study of Sirolimus in Older Children and Adults With Advanced Solid Malignancies
- ClinicalTrials.gov ID
- NCT01791088
- Acronym / sponsor ID
- 12-1169
- Conditions
- Unspecified Adult Solid Tumor, Protocol Specific, Unspecified Childhood Solid Tumor, Protocol Specific
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 13 Jun 2012 (actual)
- Primary completion
- 17 Aug 2018 (actual)
- Study completion
- 17 Aug 2018 (actual)
- First posted
- 13 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
PRIMARY OBJECTIVES:
- To describe the magnitude, inter-individual variability and time course of sirolimus-induced changes in fasting serum glucose and triglycerides.
SECONDARY OBJECTIVES:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (sirolimus) | Experimental | Drug: sirolimus, Other: pharmacological study, Other: laboratory biomarker analysisPatients receive sirolimus PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sirolimusAlso: AY 22989, Rapamune, rapamycin, SLMGiven PO | Drug | Treatment (sirolimus) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (sirolimus) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (sirolimus) |
Primary outcome
Change in fasting glucose and fasting triglycerides
Time frame: Baseline to 8 days
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.
Change in fasting glucose and fasting triglycerides
Time frame: Baseline to 15 days
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.
Change in fasting glucose and fasting triglycerides
Time frame: Baseline to 29 days
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.
4 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manish R Sharma, MD principal investigator
University of Chicago Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sirolimus, pharmacological study and laboratory biomarker analysis in people with Unspecified Adult Solid Tumor, Protocol Specific and Unspecified Childhood Solid Tumor, Protocol Specific, run by University of Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in fasting glucose and fasting triglycerides (time frame: Baseline to 8 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2019.