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Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00368914

Sirolimus in Treating Patients With Metastatic or Unresectable Solid Tumors

A Phase 1 study testing sirolimus, laboratory biomarker analysis and pharmacological study in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of sirolimus in treating patients with metastatic or unresectable solid tumors. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
sirolimus, laboratory biomarker analysis and pharmacological study
Type of treatment
Surgery or procedure
How many people
30 participants
Where
1 siteUnited States
Study dates
Dec 2004to Jun 2009
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed solid tumor malignancy
  • Metastatic or inoperable disease
  • Failed curative or standard palliative therapy OR no such therapy exists
  • Evaluable or measurable disease
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
  • Tumor amenable to serial biopsies
  • No known brain metastases

PATIENT CHARACTERISTICS:

  • ECOG 0-1
  • Life expectancy ≥ 3 months
  • WBC > 3,500/mm³
  • Absolute neutrophil count > 1,500/mm³
  • Hemoglobin > 9 g/dL
  • Creatinine ≤ 2.0 mg/dL
  • Bilirubin ≤ 2 mg/dL
  • ALT and AST ≤ 5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 5 times ULN
  • Triglycerides < 2 times ULN
  • Total cholesterol < 2 times ULN
  • Willing to undergo serial tumor biopsies and normal skin biopsies
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No immunodeficiency
  • No gastrointestinal tract disease resulting in an inability to take oral medication
  • No requirement for IV alimentation
  • No active peptic ulcer disease
  • No active infections
  • No other uncontrolled medical conditions that could potentially increase the risk of toxicities or complications of this therapy
  • No concurrent or second malignancy within the past 5 years
  • No clinically significant cardiovascular disease, including any of the following:
  • Myocardial infarction within the past 12 months
  • Unstable angina
  • Peripheral vascular disease ≥ grade 2
  • Uncontrolled congestive heart failure
  • Uncontrolled hypertension (i.e., systolic blood pressure [BP] > 170 mm Hg, diastolic BP > 95 mm Hg)

PRIOR CONCURRENT THERAPY:

  • Recovered from prior anticancer therapy
  • No unresolved chronic toxicity > CTC grade 2
  • No prior surgical procedures affecting absorption
  • More than 4 weeks since prior surgery except minor procedures (e.g., dental work or skin biopsy)
  • More than 1 month since prior participation in an investigational drug trial
  • More than 1 month since prior chemotherapy
  • No concurrent use of any of the following:
  • Phenytoin
  • Carbamazepine
  • Barbiturates
  • Rifampin
  • Phenobarbital
  • Cyclosporine
  • Clarithromycin
  • Diltiazen
  • Clotrimazole
  • Ketoconazole
  • Fluconazole
  • Hypericum perforatum (St. John's wort)
  • Cimetidine
  • Grapefruit juice
  • No concurrent immunosuppressants
  • No other concurrent investigational or commercial agents or therapies for this malignancy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

Other trials in United States

About this study

Official title: Pharmacodynamic-Guided Dose Finding Study of Rapamycin (Rapamune®, Sirolimus) in Adult Patients With Solid Tumors

RATIONALE: Sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of sirolimus in treating patients with metastatic or unresectable solid tumors.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the pharmacodynamic optimal dose of sirolimus, by evaluating p70^s6 kinase inhibition in peripheral blood mononuclear cells (PBMC) and normal skin, in patients with metastatic or unresectable solid tumors.
  • Correlate target inhibition in tumor tissue with PBMC and normal skin target inhibition in patients whose tumors are amenable to sequential tumor biopsies.

Secondary

  • Characterize the pharmacokinetics of sirolimus in these patients
  • Determine the pharmacodynamic effects of sirolimus on tumor, normal skin, and normal oral mucosa of these patients
  • Correlate the pharmacodynamic effects of sirolimus with pharmacokinetics and clinical effects.
  • Correlate the Akt signaling pathway with pharmacodynamic endpoints.
  • Explore pharmacokinetic-pharmacodynamic and toxicodynamic relationships of sirolimus in these patients.
  • Quantify the toxicity of sirolimus in these patients.
  • Evaluate, preliminarily, the activity of sirolimus in these patients.

OUTLINE: This is a prospective, dose-escalation study.

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

Cohorts of 3-6 patients receive escalating doses of sirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity. The pharmacodynamic optimal dose is considered the dose at which 10 patients are treated without requiring further dose escalation.

Patients undergo blood collection, tumor tissue and normal skin biopsies, and oral mucosal smears periodically for pharmacodynamic, pharmacokinetic, and biomarker correlative studies.

After completion of study treatment, patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Being tested
sirolimus, laboratory biomarker analysis, pharmacological study, biopsy
Keywords
unspecified adult solid tumor, protocol specific

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pharmacodynamic optimal dose of sirolimus by evaluation of p70s6 kinase inhibition in peripheral blood mononuclear cells (PBMC) and normal skin

  2. Correlation of target tissue inhibition in tumor tissue with PMBCs and normal skin

Secondary outcomes (9)

  1. Pharmacokinetics

  2. Pharmacodynamic effects of sirolimus on tumor, normal skin, and normal oral mucosa

  3. Correlation of pharmacodynamic effects of sirolimus with pharmacokinetics and clinical effects

  4. Pharmacokinetic-pharmacodynamic and toxicodynamic relationships

  5. Correlation of activation of the mTOR pathway in tumor tissue with the antitumor effects of sirolimus

  6. Toxicity by NCI Common Toxicity Criteria Version 3.0

  7. Activity of sirolimus

  8. Response rate by RECIST criteria

  9. Overall survival and progression-free survival by Kaplan-Meier method at 6 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Aug 2006 (estimated)
  2. Study startDec 2004
  3. Primary completionJun 2009
  4. Study completionJun 2009

Resources

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
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00368914
Sponsor's protocol ID
JHOC-J0402, CDR0000491204
Other IDs
R21CA112919, P30CA006973, JHOC-J0402, JHOC-04032602
Status last verified
Aug 2010
First submitted
24 Aug 2006
Last updated
9 Aug 2010
Results posted
No

Publications

  • Jimeno A, Rudek MA, Kulesza P, Ma WW, Wheelhouse J, Howard A, Khan Y, Zhao M, Jacene H, Messersmith WA, Laheru D, Donehower RC, Garrett-Mayer E, Baker SD, Hidalgo M. Pharmacodynamic-guided modified continuous reassessment method-based, dose-finding study of rapamycin in adult patients with solid tumors. J Clin Oncol. 2008 Sep 1;26(25):4172-9. doi: 10.1200/JCO.2008.16.2347.

    PubMed 18757332

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing sirolimus, laboratory biomarker analysis and pharmacological study in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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?

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 9 Aug 2010. 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?

Pharmacodynamic optimal dose of sirolimus by evaluation of p70s6 kinase inhibition in peripheral blood mononuclear cells (PBMC) and normal skin. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00368914, which also lists 1 linked publication.

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 9 Aug 2010.

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