A Randomized Discontinuation Trial to Determine the Clinical Benefit of Continuation of Sorafenib Following Disease Progression in Patients With Advanced Renal Cell Carcinoma

Inclusion Criteria:

- Male or female patients above 18 years of age with advanced RCC who have received
sorafenib as their first and only systemic anti-tumor therapy for RCC prior to
randomization

- Patients must have previously tolerated a minimum dose of sorafenib 400 mg daily for
at least six weeks prior to study entry and have radiographically documented
progressive disease while on sorafenib

- Patients must have experienced clinical benefit, partial response, complete response
or stable disease during their previous course of sorafenib therapy

- Life expectancy > 12 weeks

- Patients must meet the Memorial Sloan-Kettering Cancer Center (MSKCC) risk category
of low or medium at randomization

- Patients must give written informed consent prior to any study specific screening
procedures with the understanding that the patient has the right to withdraw from the
study at any time, without prejudice

- Patients must have at least one uni-dimensional measurable lesion by CT-scan or MRI
according to Response Evaluation Criteria in Solid Tumors (RECIST)

- Patients must not have brain metastases

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1

- In addition, the following patients may be included, provided all other inclusion and
exclusion criteria are met

- Patients who have received the vaccines cG250 (monoclonal antibody to carbonic
anhydrase IX) or HSPPC-96 (Heat Shock Protein Peptide Complex 96) are eligible
provided that they have received no other systemic anti-cancer therapy

- Patients who were enrolled in the ARCCS treatment protocol

Exclusion Criteria:

- Patients must not have experienced more than three weeks from documented disease
progression to randomization

- Any medical condition requiring the use of systemic corticosteroids during IFN
therapy

- Previous or concurrent cancer that is distinct in primary site or histology from the
cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal
cell carcinoma, superficial bladder tumors (Ta, Tis & T1) or any cancer curatively
treated within the last three years prior to study entry

- Severe renal impairment or receiving dialysis

- More than a two week interruption in sorafenib dosing immediately prior to
randomization

- Patients with a best response of disease progression on their previous course of
sorafenib

- Patients who meet the MSKCC high risk category at randomization

- Hemorrhagic episode >= Grade 2 NCI CTC AE v3.0 within last six months

- History of cardiac disease: congestive heart failure> NYHA class 2; active
cardiovascular disease (MI more than six months prior to study entry is allowed);
cardiac arrhythmia requiring anti-arrhythmic therapy (beta blockers or digoxin are
permitted) or uncontrolled hypertension

- Active clinically serious bacterial or fungal infections (>= Grade 2 NCI CTCAE v3.0)

- Known history of Human Immunodeficiency Virus (HIV) infection or chronic hepatitis B
or C

- Symptomatic metastatic brain or meningeal tumors unless the patient is > six months
from definitive therapy, has a negative CNS imaging study within four weeks of study
entry, and is clinically stable off steroids. The patient must not be undergoing
acute steroid taper

- Patients with seizure disorder requiring medication (such as steroids or
anti-epileptics)

- Ongoing substance abuse, medical, psychological or social conditions that may
interfere with the patients participation in the study or evaluation of the study
results

- Known or suspected allergy to the investigational agent or any agent given in
association with this trial, including history of sensitivity to E. coli-derived
products

- Any condition that is unstable or that could jeopardise the safety of the patient and
his/her compliance in the study. Patients with a history of severe depression;
patients with clinically significant active autoimmune disorders; history of organ
allograft

- Pregnant or breast-feeding patients. Women of childbearing potential must have a
negative pregnancy test performed within seven days of the start of study treatment.
Both men and women enrolled in this trial must use adequate birth control measures
during the course of the trial

- Patients who have had a significant surgical procedure within the past four weeks are
excluded

Excluded Therapies and Medications, Previous and Concomitant:

- Any prior or concurrent systemic anti-cancer therapy including chemotherapy,
monoclonal antibodies, hormonal therapy or investigational therapy, except for
bisphosphonates and sorafenib

- Biological response modifiers, such as G-CSF or GM-CSF, within three weeks prior to
study entry or during study. G-CSF and other hematopoietic growth factors may only
be used in the management of acute toxicity such as febrile neutropenia when
medically indicated or at the discretion of the Investigator. However, they may not
be substituted for a required dose reduction of any study drug

- Patients taking erythropoietin are permitted provided no dose adjustment is
undertaken within two months prior to the study or during the study

- Concomitant rifampicin or St. John's Wart

- Palliative therapy will be allowed, patients may receive palliative and supportive
care for any underlying illness