Sorafenib in Treating Patients With Metastatic or Unresectable Kidney Cancer

NCT ID: NCT00496756

Last Updated: 2023-10-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-01
• Study Completion Date: 2014-04-25

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.

Conditions

Kidney Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

Sorafenib

Intervention Type: DRUG

initial dose of Sorafenib will be administered orally with a dose of 400 mg twice a day, daily.Intrapatient dose escalation will occur providing no dose limiting toxicity (Grade 3 or 4) is observed. Dose level 2 600mg. Dose level 2 800mg

Interventions

Sorafenib

initial dose of Sorafenib will be administered orally with a dose of 400 mg twice a day, daily.Intrapatient dose escalation will occur providing no dose limiting toxicity (Grade 3 or 4) is observed. Dose level 2 600mg. Dose level 2 800mg

Intervention Type: DRUG

Other Intervention Names

Nexavar

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: collaborator

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ralph Hauke, MD

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

University of Nebraska Medical Center

Omaha, Nebraska, United States

Countries

United States

Other Identifiers

P30CA036727

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0081-06-FB

Identifier Type: -

Identifier Source: org_study_id