Sirolimus in Treating Patients With Metastatic or Unresectable Solid Tumors

NCT00368914 | Completed Phase 1

• 5 other identifiers: JHOC-J0402, CDR0000491204R21CA112919P30CA006973JHOC-J0402JHOC-04032602
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (2)

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

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

Secondary Outcomes (9)

• Pharmacokinetics

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

• Correlation of pharmacodynamic effects of sirolimus with pharmacokinetics and clinical effects

• Pharmacokinetic-pharmacodynamic and toxicodynamic relationships

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

Interventions

sirolimus DRUG

laboratory biomarker analysis OTHER

pharmacological study OTHER

biopsy PROCEDURE

Eligibility Criteria

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

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Related Publications (1)

• 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.

  PMID: 18757332 RESULT

MeSH Terms

Interventions

Sirolimus; Biopsy

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Manuel Hidalgo, MD, PhD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 24, 2006
• First Posted: August 29, 2006
• Study Start: December 1, 2004
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: August 9, 2010

Record last verified: 2010-08

Locations

US (1)