We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

Sirolimus in Treating Patients With Metastatic or Unresectable Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00368914
Recruitment Status : Completed
First Posted : August 29, 2006
Last Update Posted : August 9, 2010
National Cancer Institute (NCI)
Information provided by:
Sidney Kimmel Comprehensive Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: sirolimus Other: laboratory biomarker analysis Other: pharmacological study Procedure: biopsy Phase 1

Detailed Description:



  • 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.


  • 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Primary Purpose: Treatment
Official Title: Pharmacodynamic-Guided Dose Finding Study of Rapamycin (Rapamune®, Sirolimus) in Adult Patients With Solid Tumors
Study Start Date : December 2004
Primary Completion Date : June 2009
Study Completion Date : June 2009

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  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 Outcome Measures :
  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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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)


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00368914

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Manuel Hidalgo, MD, PhD Sidney Kimmel Comprehensive Cancer Center

ClinicalTrials.gov Identifier: NCT00368914     History of Changes
Other Study ID Numbers: JHOC-J0402, CDR0000491204
R21CA112919 ( U.S. NIH Grant/Contract )
P30CA006973 ( U.S. NIH Grant/Contract )
First Posted: August 29, 2006    Key Record Dates
Last Update Posted: August 9, 2010
Last Verified: August 2010

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs