Sorafenib in Treating Patients With Metastatic or Unresectable Kidney Cancer

Phase 2

Terminated

Conditions: Kidney Cancer

Interventions: Drug: Sorafenib

Registration Number: NCT00496756

Lead Sponsor: University of Nebraska

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 14

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sorafenib	Sorafenib	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.

Primary Outcome Measures

Name	Time	Method
Toxicity of Intrapatient Dose Escalation of Sorafenib Tosylate	Study completion	To evaluate the toxicity of dose escalating sorafenib, an estimation of the percentage of patients who are unable to tolerate those escalated doses will be made. Patients will be dose escalated every 4 weeks until a maximum dose of 800 mg BID is reached.

Secondary Outcome Measures

Name	Time	Method
Response Rate	from the start of the treatment until disease progression/recurrence	The proportion of subjects with an objective response of complete or partial based on the RECIST Criteria