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. Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving everolimus together with combination chemotherapy and/or panitumumab may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with fluorouracil, leucovorin, panitumumab, and oxaliplatin in treating patients with solid tumors that did not respond to previous treatment.

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of everolimus in combination with sequential fluorouracil (5-FU) and leucovorin calcium, panitumumab, modified 5-FU, leucovorin calcium, and oxaliplatin (mFOLFOX6), and mFOLFOX6 with panitumumab in patients with refractory solid tumors.

Secondary

• To determine the adverse event profile of these regimens.
• To correlate response with S6-phosphorylation and AKT-phosphorylation in available archived tumor samples.
• To evaluate preliminary evidence of antitumor activity of these regimens using RECIST criteria for a subset of patients with measurable disease.

OUTLINE: This is a dose-escalation study. Cohorts of patients are enrolled into treatment groups 1 or 2. If a final cohort of patients is reached in groups 1 and/or 2, additional cohorts of patients are enrolled into treatment group 3.

• Group 1: Patients receive oral everolimus once daily on days 1-28. Patients also receive leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
• Group 2: Patients receive oral everolimus once daily on days 1-28 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
• Group 3: Patients receive oral everolimus once daily on days 1-28, leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1, and oxaliplatin IV over 2-4 hours on day 1. Some patients may also receive panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Archived tumor samples are assessed for phospho-AKT, phospho-S6K, and phospho-S6 by immunohistochemistry.

After completion of study treatment, patients are followed every 3 months for 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant solid tumor

  • Advanced or unresectable disease

• No standard therapeutic option available

• Evaluable disease (according to RECIST criteria) that has not been previously irradiated

  • Prior radiotherapy to the marker lesion(s) allowed provided there is evidence of progression since radiotherapy

• Brain metastases allowed provided the following criteria are met:

  • CNS-directed treatment was given and was completed > 3 months ago
  • CNS disease has been clinically and radiographically stable for ≥ 8 weeks

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,500/µL
• Platelet count ≥ 100,000/µL
• Creatinine clearance ≥ 60 mL/min
• Total bilirubin ≤ 1.2 mg/dL
• Transaminases ≤ 5 times upper limit of normal (ULN)
• Magnesium ≥ lower limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 24 weeks (females) or for 4 weeks (males) after completion of study therapy
• Willing to avoid pregnancy for 3 months after completion of study therapy
• No neuropathy ≥ grade 2
• No concurrent life-threatening acute medical illness
• No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• No active bleeding diathesis

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 3 weeks since prior major surgery, radiotherapy (including radiotherapy involving the abdomen or spine), chemotherapy, or other systemic anticancer therapy and recovered
• At least 4 weeks since prior investigational drugs
• No concurrent CYP3A4 inducers or inhibitors that cannot be substituted by a different agent
• No concurrent oral anti-vitamin K medication (except for low-dose warfarin)
• No concurrent colony stimulating factors during the first course of treatment