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
Condition: HLRCC; Sporadic Papillary Renal Cell Cancer
MeSH terms: Carcinoma, Renal Cell; Leiomyomatosis; Neoplastic Syndromes, Hereditary; Skin Neoplasms; Uterine Neoplasms
Intervention: Bevacizumab; Erlotinib
Intervention description: Commercially available. Administered by intravenous infusion.; Commercially available. Administered orally.
Intervention MeSH terms: Bevacizumab; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 83.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immunotherapy; Biomarker; Kidney Cancer; Renal Cell Cancer; Hereditary Leiomyomatosis and Renal Cell Cancer; HLRCC

Summary:

      Background:

        -  At the present time, there are no drugs that have been proven to work in patients with
           papillary kidney cancer that has spread (metastasized) beyond the kidneys. Researchers
           are interested in determining whether the combination of the drugs bevacizumab and
           erlotinib can be used to treat metastatic papillary kidney cancer.

        -  Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) is an inherited type of
           papillary kidney cancer (it runs in families). Papillary kidney cancer can also occur
           sporadically, or without a family connection. More research is needed to determine
           whether treatments for papillary kidney cancer, such as bevacizumab and erlotinib, work
           in inherited or sporadic types of kidney cancer, and if so, whether there are any
           differences.

      Objectives:

      -To determine the effectiveness of the combination of bevacizumab and erlotinib as a
      treatment for patients with (1) metastatic HLRCC kidney cancer and (2) metastatic kidney
      cancer not associated with HLRCC (or sporadic papillary RCC).

      Eligibility:

        -  Individuals 18 years of age or older who have been diagnosed with papillary kidney
           cancer that has spread beyond the kidneys.

        -  Participants may have either HLRCC or sporadic papillary kidney cancer.

      Design:

        -  Participants will be screened with a full medical history, physical examination, blood
           and urine tests, and computed tomography (CT) and other scans to evaluate tumor size and
           treatment options.

        -  Participants will receive 28-day treatment cycles of bevacizumab (given intravenously
           every 2 weeks) and erlotinib (a tablet taken by mouth daily).

        -  Every cycle, participants will return for regular blood and urine tests. Every other
           cycle, participants will have imaging scans to assess tumor size and response to
           treatment. Female participants who have uterine fibroid tumors related to their kidney
           cancer may have additional scans to assess tumor size and response to treatment.

        -  Participants will continue to receive treatment on the study until their tumors grow or
           spread to new areas (disease progression), intolerable side effects develop, a better
           treatment option becomes available, the study closes, it is unsafe to continue
           treatment, or the participant decides not to remain in the study.
    

Eligibility criteria:

        -  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.