Clinical trial NCT00496756: Sorafenib in Treating Patients With Metastatic or Unresectable Kidney Cancer
Official title: A Phase II Study of Sorafenib in Patients With Metastatic Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Kidney Cancer
Keywords: clear cell renal cell carcinoma
stage III renal cell cancer
stage IV renal cell cancer
recurrent renal cell cancer
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Bayer
First posted: 2007-07-04
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 criteria: DISEASE CHARACTERISTICS:

Inclusion Criteria:

* Histologically or cytologically confirmed renal cell carcinoma (RCC)

  * Must have a component of conventional clear cell RCC
  * Predominant clear cell component ≥ 75%
* Metastatic or unresectable 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)
* Measurable or nonmeasurable disease, includes any of the following:

  * Small lesions, 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
* Karnofsky performance status 70-100%
* 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
* At least 4 weeks since prior major surgery and/or radiotherapy and recovered
* 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

Exclusion Criteria:

* Patients with true papillary, sarcomatoid features without any clear cell component, chromophobe, oncocytoma, collecting duct tumors, or transitional cell carcinoma are not eligible
* No evidence of CNS metastases
* No imaging (MRI or CT scan of the brain) abnormality indicative of CNS metastases within past 42 days
* Not pregnant or nursing (negative pregnancy test)
* 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)
* No more than one prior systemic therapy for RCC
* No prior vascular endothelial growth factor receptor agents
* No concurrent systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency)

  o Topical and/or inhaled steroids allowed
* No concurrent full-dose oral or parenteral anticoagulation

  o 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 o Concurrent hormones administered for non-disease related conditions (e.g., insulin for diabetes) allowed

Primary outcomes:
measure: Toxicity of Intrapatient Dose Escalation of Sorafenib Tosylate
timeFrame: Study completion
Secondary outcomes:
measure: Response Rate
timeFrame: from the start of the treatment until disease progression/recurrence
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Ralph Hauke, MD
role: PRINCIPAL_INVESTIGATOR
References: