Sorafenib in Treating Patients With Metastatic or Unresectable Kidney Cancer

University of Nebraska

Status and phase: Terminated; Phase 2

Conditions: Kidney Cancer

Treatments: Drug: Sorafenib

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00496756

0081-06-FB

P30CA036727 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 14 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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14 participants in 1 patient group

Sorafenib

Other group

Description:

The initial dose of Sorafenib will be administered orally with a dose of 400 mg twice a day, daily. Intrapatient dose escalation will occur as defined in the table below, providing no dose limiting toxicity (Grade 3 or 4) is observed. If grade 3 or 4 toxicity is observed, delay and dose modification will occur as defined in protocol. Once dose level 3 is reached, the patient will remain at that dose as defined in following section. Dose Level 1 Day 1-28 400 mg b.i.d. Dose Level 2 Day 29-56 600 mg b.i.d. Dose Level 3 Day 57- 800 mg b.i.d. A treatment cycle will be 4 weeks. Two 4-week cycles will be administered. At the completion of two cycles (week 8), restaging will occur. Patients will continue on therapy per study protocol.

Treatment:

Drug: Sorafenib