Erlotinib in Treating Patients With Advanced Kidney Cancer
Condition: Kidney Cancer
MeSH terms: Kidney Neoplasms; Carcinoma, Renal Cell
Intervention: OSI-774
Intervention description: OSI-774 is an orally active, potent, selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase.
Intervention MeSH terms: Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent renal cell cancer; stage III renal cell cancer; stage IV renal cell cancer

Summary:

      RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for
      tumor cell growth.

      PURPOSE: Phase II trial to study the effectiveness of erlotinib in treating patients who have
      advanced kidney cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed diagnosis of advanced
             renal cell carcinoma (RCC). Papillary RCC is permitted only if immunohistochemical
             evidence of strong (2-3+) EGFR expression.

          -  Disease that is recurrent or refractory to IL-2 or IFN-based therapy or new diagnosis
             in previously untreated patients who are not appropriate candidates to receive IL-2
             -based treatment

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >20
             mm with conventional techniques or as >10 mm with spiral CT scan.

          -  Prior nephrectomy or resection of metastatic lesions permitted if full surgical
             recovery has occurred.

          -  Age > 18 years Because no dosing or adverse event data are currently available on the
             use of OSI-774 in patients <18 years of age, children are excluded from this study but
             will be eligible for future pediatric single-agent trials, if applicable.

          -  Life expectancy of at least 12 weeks

          -  ECOG performance status of 0,1 or 2 or Karnofsky >60%

          -  Patients must have normal organ and marrow function as defined below:

        Hematopoietic

          1. Absolute neutrophil count at least ≥ 1,500/ul

          2. Platelet ≥ 100,000/uL

          3. Hemoglobin ≥ 9.0 g/dL, concomitant erythropoetin permitted Hepatic

        a. Total bilirubin within normal institutional limits b. AST (SGOT)/ALT (SGPT) ≤ 2.5 times
        institutional upper limit of normal (≤5 times ULN if liver metastases present) Renal

        a. Serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance > 60 mL/min/1.73m2
        Calcium

        a. Corrected calcium < 12.0 mg/dl, concomitant hypocalcemic agents permitted

          -  Complete supportive and palliative care will continue to be provided to ameliorate
             signs and symptoms that were pre-existing or may arise while on study and which do not
             interfere with the objectives of the study. The use of erythropoietin and
             biphosphonates is permitted.

          -  Patients must have tumor blocks available for EGFR expression analysis to be eligible
             for treatment on this study.

        Exclusion Criteria:

          -  History of active malignancy (other than RCC) in the past 3 years, other than
             nonmelanomatous skin cancer or in situ breast cancer or in situ cervical cancer.

          -  Patients with known brain metastases will be excluded from this clinical trial because
             of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier.

          -  Patients may not be receiving any other investigational agents.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to OSI-774.

          -  Prior treatment with EGFR targeting therapies.

          -  Inability to understand the written informed consent document.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Major surgery, or significant traumatic injury occurring within 21 days prior to
             treatment.

          -  Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren's
             syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp
             examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal
             corneal sensitivity test (Schirmer test or similar tear production test).

          -  Gastrointestinal tract disease resulting in an inability to take oral medication or a
             requirement for IV alimentation, prior surgical procedures affecting absorption, or
             active peptic ulcer disease.

          -  Pregnant women are excluded from this study because OSI-774 is an epidermal growth
             factor inhibitor with the potential for teratogenic or abortifacient effects based on
             the data suggesting that EGFR expression is important for normal organ development.
             For this reason, women of childbearing potential and men must also agree to use
             adequate contraception (hormonal or barrier method of birth control) prior to study
             entry and for the duration of study participation. Should a woman become pregnant or
             suspect she is pregnant while participating in this study, she should inform her
             treating physician immediately. Because there is an unknown but potential risk for
             adverse events in nursing infants secondary to treatment of the mother with OSI-774,
             breastfeeding should be discontinued if the mother is treated with OSI-774.

          -  Because patients with immune deficiency are at increased risk of lethal infections
             when treated with marrow-suppressive therapy, HIV-positive patients receiving
             combination anti-retroviral therapy are excluded from the study because of possible
             pharmacokinetic interactions with OSI-774. Appropriate studies will be undertaken in
             patients receiving combination anti-retroviral therapy when indicated.

          -  Informed Consent - No study specific procedures will be performed without a written
             and signed informed consent document. Patients who do not demonstrate the ability to
             understand or the willingness to sign the written informed consent document are
             excluded from study entry.