Everolimus in Treating Patients With Advanced or Metastatic Colorectal Cancer That Did Not Respond to Previous Therapy

Phase 2

Terminated

Brief Summary: 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.

Detailed Description: OBJECTIVES:

* 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Primary Outcome Measures

Name	Time	Method
Response Rate: The Total Number of Participants With Progression of Disease	1 month	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.

Secondary Outcome Measures