Everolimus in Treating Patients With Advanced or Metastatic Colorectal Cancer That Did Not Respond to Previous Therapy
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PURPOSE: This phase II trial is studying how well everolimus works in treating patients with advanced or metastatic colorectal cancer that did not respond to previous therapy.
Procedure: antiangiogenesis therapy
Procedure: diagnostic procedure
Procedure: gene expression analysis
Procedure: immunohistochemistry staining method
Procedure: laboratory biomarker analysis
Procedure: mutation analysis
Procedure: protein tyrosine kinase inhibitor therapy
Procedure: reverse transcriptase-polymerase chain reaction
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Single Agent RAD001 in Patients With Colon Cancer and Activating Mutations in the PI3KCA Gene|
- Response Rate: The Total Number of Participants With Progression of Disease [ Time Frame: 1 month ] [ Designated as safety issue: No ]
To determine response rate and time to tumor progression of patients with colorectal cancer and mutations in the PI3KCA gene who are treated with RAD001. Response and progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions assessed by CT (or MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesion. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesion.
The outcome measure will be the total number of subjects who show progression of disease.
|Study Start Date:||October 2006|
|Study Completion Date:||October 2007|
|Primary Completion Date:||October 2007 (Final data collection date for primary outcome measure)|
- Determine response rate, time to tumor progression, and survival of patients with advanced or metastatic refractory colorectal cancer and mutations in the PI3K gene treated with everolimus.
- Determine the toxicity profile of this drug in these patients.
- Measure the signaling pathways activated in these patients.
- Determine the pharmacodynamic effects of this drug in these patients.
OUTLINE: This is an open-label study.
Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo tumor biopsies and normal skin biopsies at baseline and after the first course of study treatment. Tumor tissue is examined for biological markers (e.g., epidermal growth factor receptor, ERK, Akt, p70s6k, p27, and Rb protein) by immunohistochemistry; apoptosis quantification by TUNEL assay; Ki-67 quantification and Ki-index; gene expression; and c-fos and p27 expression by reverse-transcriptase polymerase chain reaction.
PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00390364
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|Principal Investigator:||Manuel Hidalgo, MD, PhD||Sidney Kimmel Comprehensive Cancer Center|