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

• Status: Terminated
• Trial end date: 2007-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: National Cancer Institute (NCI)
• Treatments: Everolimus; Sirolimus

Criteria

DISEASE CHARACTERISTICS:

• Cytologically or pathologically confirmed colorectal adenocarcinoma

• Advanced or metastatic disease

• Refractory to ≥ 1 line of prior therapy

• Not amenable to potentially curative surgical resection

• Mutations in the PI3K gene in tumor tissue

• Tumor tissue available for genetic testing OR willing to undergo baseline tumor biopsy

• Tumor amenable to sequential biopsies

• Willing to undergo 2 sequential tumor biopsies, and 2 sequential skin biopsies

• Measurable lesion with ≥ 1 diameter ≥ 2 cm by conventional CT scan (1 cm by spiral CT scan) in a nonirradiated area

• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

• Life expectancy > 12 weeks

• WBC ≥ 3,000/mm³

• Absolute neutrophil count ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Bilirubin normal

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)

• Creatinine normal OR creatinine clearance ≥ 60 mL/min

• Cholesterol and triglycerides ≤ 2.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus

• No uncontrolled intercurrent illness, including, but not limited to, any of the following:

• Hypertension

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness or social situation that would preclude study compliance

• No evidence of bleeding diathesis

• Able to swallow tablets

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered

• No prior targeted therapy against mTOR

• No other concurrent investigational agents

• No concurrent therapeutic anticoagulation

• Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices allowed provided the requirements for PT, INR or PTT are met.

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent anticancer therapy, including chemotherapy, hormonal therapy, immunotherapy, alternative therapy, or radiotherapy

• No concurrent live vaccination