This randomized phase I/II trial studies the side effects, best way to give, and best dose of erlotinib and bevacizumab when given with cetuximab and how well giving erlotinib and cetuximab together with or without bevacizumab works in treating patients with metastatic or unresectable kidney, colorectal, head and neck, pancreatic, or non-small cell lung cancer. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab and bevacizumab, 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. Cetuximab and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving erlotinib together with cetuximab and/or bevacizumab may kill more tumor cells.

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of erlotinib when combined with cetuximab in patients with metastatic or unresectable renal cell, colorectal, head and neck, pancreatic, or non-small cell lung cancer (part 1).

II. Determine the MTD of bevacizumab when combined with cetuximab and erlotinib in these patients (part 2).

III. Determine the toxic effects, both quantitatively and qualitatively, of these regimens in these patients.

IV. Determine the antitumor activity of these regimens, in terms of tumor response, short-term survival, and progression-free survival, in these patients.

SECONDARY OBJECTIVES:

I. Compare, preliminarily, the toxicity and antitumor activity profiles of these regimens in these patients.

OUTLINE: This is an open-label, multicenter, dose-escalation study of erlotinib and bevacizumab.

Part 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22.

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Part 2: Patients receive erlotinib as in part 1 at the MTD and cetuximab as in part 1. Patients also receive bevacizumab IV over 1½ hours on day 1 and over 1 hour on day 15.

Cohorts of 3-6 patients receive escalating doses of bevacizumab until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

In both groups, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

After completion of study treatment, patients are followed at 1 month.

Inclusion Criteria:

• One of the following histologically confirmed diagnoses:

  • Renal cell cancer

    • Clear cell histology

    • Metastatic or unresectable disease AND meets 1 of the following criteria:

      • Recurrent disease
      • Refractory to interleukin-2 (IL-2)- or interferon-based therapy
      • Previously untreated AND not a candidate for IL-2-based therapy

  • Colorectal, head and neck, pancreatic, or non-small cell lung cancer

    • Metastatic or unresectable disease
    • Progression after prior standard treatment

• No evidence of CNS disease, including the following (part 2 only):

  • Primary brain tumor
  • Brain metastases

• Paraffin embedded tumor blocks available

• Performance status - ECOG 0-2

• Performance status - Karnofsky 60-100%

• More than 12 weeks

• Absolute neutrophil count ≥ 1,500 mm^3

• Platelet count ≥ 100,000 mm^3

• Bilirubin ≤ 1.5 mg/dL

• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastasis is present)

• PTT and INR ≤ 1.5, unless receiving full-dose warfarin (part 2 only)

• Creatinine ≤ 1.5 times ULN

• Creatinine clearance ≥ 60 mL/min

• Calcium < 10 mg/dL (hypocalcemic agents allowed)

• No proteinuria*

• Protein < 1 g on 24-hour urine collection*

• No unstable angina pectoris

• No cardiac arrhythmia

• No symptomatic congestive heart failure

• None of the following are allowed for part 2:

  • Myocardial infarction within the past 6 months
  • New York Heart Association class II-IV heart disease
  • Serious cardiac arrhythmia requiring medication
  • Peripheral vascular disease ≥ grade II
  • Recent history of cerebrovascular accident
  • Uncontrolled hypertension (blood pressure ≥ 150/85 mm Hg despite medication)
  • Other clinically significant cardiovascular disease

• No gastrointestinal (GI) tract disease resulting in an inability to take oral medication

• No GI tract disease resulting in a requirement for IV alimentation

• No active peptic ulcer disease

• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drugs

• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (part 2 only)

• No ongoing or active infection

• No active infection requiring parenteral antibiotics (part 2 only)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 2 months after study treatment

• No significant traumatic injury within the past 28 days (part 2 only)

• No history of abnormalities of the cornea (e.g., dry eye syndrome, Sjögren's syndrome, or congenital abnormality [e.g., Fuch's dystrophy])

• No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the breast or cervix

• No psychiatric illness or social situation that would preclude study compliance

• No serious or non-healing wound ulcer or bone fracture (part 2 only)

• No other uncontrolled illness

• See Disease Characteristics

• More than 4 weeks since prior immunotherapy

• No prior cetuximab

• No prior bevacizumab

• Concurrent epoetin alfa or darbepoetin alfa allowed

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

• More than 4 weeks since prior radiotherapy

• No prior surgical procedures affecting absorption

• Prior nephrectomy or resection of metastatic lesions allowed provided patient has fully recovered

• More than 7 days since prior core biopsy*

• More than 28 days since prior major surgery or open biopsy*

• No concurrent major surgery*

• Recovered from all prior therapy

• No prior erlotinib

• Concurrent bisphosphonates allowed

• Concurrent full-dose anticoagulants allowed provided the following criteria are met (part 2 only):

  • In-range INR (usually between 2 and 3) AND on a stable dose of warfarin or low molecular weight heparin
  • No active bleeding
  • No pathological conditions that carry a high risk of bleeding (e.g., tumor involving major vessels or varices)

• No other concurrent investigational agents

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent anticancer therapy