Patient case: 46-year-old female with papillary thyroid carcinoma; genetic feature: NTRK1

Clinical trial: Sorafenib in Treating Patients With Metastatic or Unresectable Kidney Cancer

Summary: RATIONALE: Sorafenib 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.
  PURPOSE: This phase II trial is studying the side effects and how well sorafenib works in treating patients with metastatic or unresectable kidney cancer.

Detailed description: OBJECTIVES:
  Primary
  -  Evaluate the safety and toxicity of dose escalating sorafenib tosylate in patients with metastatic or unresectable renal cell carcinoma.
  Secondary
  -  Determine tumor response in these patients.
  -  Determine time to progression in these patients.
  -  Determine overall survival of these patients.
  Tertiary
  -  Collect data on angiogenesis inhibition induced by sorafenib tosylate.
  -  Collect data on immunomodulatory effects of sorafenib tosylate.
  OUTLINE: This is an open-label study.
  Patients receive oral sorafenib tosylate twice daily on days 1-28. Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.
  Patients receive escalating doses of sorafenib tosylate (in the absence of grade 3 or 4 dose-limiting toxicity) until a pre-determined dose is reached.
  Blood and urine samples are collected at baseline and periodically during study for VEGF level determination. Blood samples are analyzed for T4/T8, NK, CD25+, and Fox p3 by flow cytometry. Tumor tissue blocks or unstained slides are obtained for chemistry staining of VEGF.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically or cytologically confirmed renal cell carcinoma (RCC)
  -  Must have a component of conventional clear cell RCC
  -  Predominant clear cell component ≥ 75%
  -  Patients with true papillary, sarcomatoid features without any clear cell component, chromophobe, oncocytoma, collecting duct tumors, or transitional cell carcinoma are not eligible
  -  Metastatic or unresectable disease
  -  Measurable or nonmeasurable disease
  -  Measurable disease is defined as any lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan or MRI
  -  Nonmeasurable disease includes any of the following:
  -  Small lesions with longest diameter < 20 mm by conventional techniques or < 10 mm by spiral CT scan
  -  Bone lesions
  -  Leptomeningeal disease
  -  Ascites
  -  Pleural/pericardial effusion
  -  Lymphangitis cutis/pulmonitis
  -  Abdominal masses that are not confirmed and followed by imaging techniques
  -  Cystic lesions
  -  Irradiated lesions, unless progression is documented after radiotherapy
  -  Paraffin RCC tissue blocks or unstained slides must be obtained for future chemistry staining of VEGF
  -  No evidence of CNS metastases
  -  No imaging (MRI or CT scan of the brain) abnormality indicative of CNS metastases within the past 42 days
  PATIENT CHARACTERISTICS:
  -  Karnofsky performance status 70-100%
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception (hormonal and/or barrier method) during and for 3 months after completion of study treatment
  -  Granulocyte count ≥ 1,500/µL
  -  Platelet count ≥ 100,000/µL
  -  AST/ALT ≤ 2.5 times upper limit of normal (ULN)
  -  Alkaline phosphatase ≤ 2.5 times ULN
  -  Serum bilirubin ≤ 1.5 times ULN
  -  Protein ≤ 1+ by urinalysis
  -  Creatinine ≤ 1.5 times ULN
  -  No ongoing hemoptysis
  -  No cerebrovascular accident within the past 12 months
  -  No peripheral vascular disease with claudication while walking less than 1 block
  -  No history of clinically significant bleeding
  -  No deep venous thrombosis or pulmonary embolus within the past year
  -  No significant cardiovascular disease, defined as NYHA class II-IV congestive heart failure, angina pectoris requiring nitrate therapy, or myocardial infarction within the past 6 months
  -  No uncontrolled hypertension, defined as systolic BP > 160 mm Hg and/or diastolic BP > 90 mm Hg while on medication
  -  No preexisting thyroid abnormality whose thyroid function cannot be maintained in the normal range by medication
  -  No uncontrolled psychiatric disorder
  -  No delayed healing of wounds, ulcers, and/or bone fractures
  -  No currently active second malignancy except nonmelanoma skin cancer
  -  Patients are not considered to have a 'currently active' malignancy if they have completed anticancer therapy and are considered by their physician to be at less than 30% risk of relapse
  PRIOR CONCURRENT THERAPY:
  -  At least 4 weeks since prior major surgery and/or radiotherapy and recovered
  -  No more than one prior systemic therapy for RCC
  -  No prior vascular endothelial growth factor receptor agents
  -  Prior palliative radiotherapy for metastatic lesion(s) allowed provided there is at least one measurable and/or evaluable lesion(s) that has not been irradiated
  -  More than 4 weeks since prior and no other concurrent anticancer therapy
  -  Concurrent continuation of bisphosphonates allowed for bone metastases prophylaxis
  -  No concurrent systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency)
  -  Topical and/or inhaled steroids allowed
  -  No concurrent full-dose oral or parenteral anticoagulation
  -  Low-dose warfarin (1 mg) for maintenance of catheter patency or daily prophylactic aspirin allowed
  -  No concurrent Hypericum perforatum (St. John's wort)
  -  No concurrent ketoconazole, itraconazole, ritonavir, rifampin, or products containing grapefruit juice
  -  No concurrent hormonal therapy or chemotherapy
  -  Concurrent hormones administered for non-disease related conditions (e.g., insulin for diabetes) allowed

Relevance to patient case: not relevant