Everolimus in Treating Patients With Advanced or Metastatic Colorectal Cancer That Did Not Respond to Previous Therapy
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: everolimus; antiangiogenesis therapy; biopsy; diagnostic procedure; gene expression analysis; immunohistochemistry staining method; laboratory biomarker analysis; mutation analysis; protein tyrosine kinase inhibitor therapy; reverse transcriptase-polymerase chain reaction
Intervention MeSH terms: Everolimus; Tyrosine Protein Kinase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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.
    

Eligibility 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