A Phase II Study of Bevacizumab and Erlotinib in Subjects With Advanced Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) or Sporadic Papillary Renal Cell Cancer

* INCLUSION CRITERIA:

Patients must meet all the following criteria to be eligible for study enrolment:

* Diagnosis of advanced renal cell cancer (RCC) associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) (cohorts 1 \& 3) or sporadic/non-HLRCC papillary RCC (cohort 2 \& 4)
* Measurable disease outlined in Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* No more than two prior regimens targeting the vascular endothelial growth factor (VEGF) pathway; no prior bevacizumab therapy
* Age greater than or equal to 18 years.
* Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
* Patients must have normal organ and marrow function as defined below: white blood cell (WBC) count greater than or equal to 3,000/microL, absolute neutrophil count greater than or equal to 1,500/microL, platelet count greater than or equal to 100,000/microL, serum creatinine greater than or equal to 2 times the upper limit of reference range or creatinine clearance greater than or equal to 30 ml/min, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 times the upper limit of reference range, total bilirubin less than 1.5 times the upper limit of reference range ( less than 3 x upper limit of reference range in patients with Gilbert's disease), alkaline phosphatase less than or equal to 2.5 times the upper limit of reference range (or less than or equal to 5 times the upper limit of reference range if considered to be related to liver or bone metastases by the principal investigator (PI)
* Recovery from acute toxicity of prior treatment for RCC (to less than or equal to grade 1 the active version of Common Terminology Criteria for Adverse Events (CTCAE) or to a level permitted under other sections of Inclusion/ Exclusion criteria).
* At least 4 weeks from completion of major surgery and a healed surgical incision
* Negative pregnancy test (within 7 days of enrolment) in women of childbearing potential
* No myocardial infarction, gastrointestinal (GI) perforation/fistula, intra-abdominal abscess, cerebrovascular accidents within six months prior to study entry
* No coagulopathy or bleeding diathesis
* Ability to understand and the willingness to sign a written informed consent document.
* Archival tissue block or unstained tumor tissue available for correlative studies

EXCLUSION CRITERIA:

* Prior invasive malignancy of other histology, with the exception of adequately treated basal or squamous cell carcinoma of the skin, or any other malignancy for which the patient does not currently require treatment and/or has no evidence of disease for greater than or equal to 2 years.
* Patients with known brain metastases unless treated with an appropriate modality with no evidence of progression/recurrence for greater than 3 months
* Hypertension not controlled by medical therapy (resting systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg on at least two occasions over a 24 hour period despite optimal medical management).
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure (New York Heart Association grade III or greater), unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
* Serious, non-healing wound or ulcer; bone fracture within 3 months prior to study entry
* Patient known to be human immunodeficiency virus (HIV)-positive and requiring antiretroviral therapy (due to the risk of potential drug interactions)
* Concomitant therapy with potent inhibitors of Cytochrome P450 3A4 (CYP450 3A4) (e.g., ketoconazole, verapamil etc.) or with potent CYP450 1A2 inhibitors (fluoroquinolone antibiotics including ciprofloxacin, levofloxacin, and norfloxacin; ticlodipine, cimetidine, amiodarone, etc. see Appendix C)
* Pregnant women are excluded from this study because bevacizumab and erlotinib are anti-cancer agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on this study
* All men and women of childbearing potential must be willing to use effective contraception as determined by the principal investigator (including but not limited to abstinence, hormonal contraceptives (birth control pills, injections, or implants), intrauterine device (IUD), tubal ligation, vasectomy) from the time of enrolment to at least six months following the last dose of drug
* Any known hypersensitivity to bevacizumab, erlotinib or other excipients of these drugs
* Documented baseline proteinuria greater than 1000mg/day on 24-hour urine collection. Only patients with 1+ or greater proteinuria on urinalysis (UA) and a spot urine protein: creatinine ratio of greater than 0.5 will undergo a 24-hour urine collection for quantitation of proteinuria.
* Left ventricular ejection fraction less than 40% as measured on transthoracic echocardiogram.

INCLUSION OF WOMEN AND MINORITIES:

Both men and women and members of all races and ethnic groups are eligible for this trial.