Conditions: Colorectal Cancer
Keywords: adenocarcinoma of the colon adenocarcinoma of the rectum recurrent colon cancer stage III colon cancer stage IV colon cancer recurrent rectal cancer stage III rectal cancer stage IV rectal cancer
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 1
Healthy volunteers: no

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.

Arms:

Interventions: intervention 1: everolimus intervention 2: antiangiogenesis therapy intervention 3: biopsy intervention 4: diagnostic procedure intervention 5: gene expression analysis intervention 6: immunohistochemistry staining method intervention 7: laboratory biomarker analysis intervention 8: mutation analysis intervention 9: protein tyrosine kinase inhibitor therapy intervention 10: reverse transcriptase-polymerase chain reaction
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None intervention 7: None intervention 8: None intervention 9: None intervention 10: None

Protocol document: