TroVax Renal Immunotherapy Survival Trial

Inclusion Criteria:

• Signed informed consent. The patient must be competent to give written informedconsent and comply with the protocol requirements.

• Locally advanced or metastatic, histologically proven clear cell renal carcinoma.

• Primary tumour surgically removed (some residual advanced primary tumour may remain).

• At least four weeks post surgery or radiotherapy.

• First-line. No prior therapy for renal cancer except surgery or radiotherapy.

• Measurable disease.

• Aged 18 years or more.

• Patient expected to survive a minimum of 12 weeks (i.e. in the opinion of theinvestigator there is a >90% probability that the patient will survive >12 weeks iftreated with the selected standard of care).

• Free of clinically apparent autoimmune disease (including no prior confirmed diagnosisor treatment for autoimmune disease including Systemic Lupus Erythematosis, Grave'sdisease, Hashimoto's thyroiditis, multiple sclerosis, insulin dependant diabetesmellitus or systemic (non-joint) manifestations of rheumatoid disease).

• Total white cell count ≥ 3 x 109/L and lymphocyte count ≥1 x 109/L.

• Serum creatinine ≤1.5 times the upper limit of normal.

• Bilirubin ≤ 2 times the upper limit of normal and an SGPT of ≤ 4 times the upper limitof normal.

• Women must be either post menopausal, or rendered surgically sterile or, if of childbearing potential, must have been practising a reliable form of contraception (oralcontraception + a barrier method) for at least three months prior to the first dose ofTroVax® and must continue while they are being treated with TroVax®. Men must practisea reliable form of contraception (barrier or vasectomy) while they are being treatedwith TroVax®.

• No acute changes on 12-lead ECG.

• Ejection fraction documented as not less than 45% or no clinical suspicion thatcardiac ejection fraction is less than 45%.(If clinical suspicion exists the ejectionfraction should be measured according to local site procedures).

• Karnofsky performance status of ≥ 80%.

Exclusion Criteria:

• Cerebral metastases. (Known from previous investigations or clinically detectable).

• Previous exposure to TroVax®.

• Serious infections within the 28 days prior to entry to the trial.

• Known to test positive for HIV or hepatitis B or C.

• Life threatening illness unrelated to cancer.

• History of allergic response to previous vaccinia vaccinations.

• Known allergy to egg proteins.

• Known hypersensitivity to neomycin.

• Participation in any other clinical trial of a licensed or unlicensed drug within theprevious 30 days or during the course of this trial.

• Previous malignancies within the last 10 years other than successfully treatedsquamous carcinoma of the skin or in situ carcinoma of the cervix treated with conebiopsy.

• Previous history of major psychiatric disorder requiring hospitalization or anycurrent psychiatric disorder that would impede the patient's ability to provideinformed consent or to comply with the protocol.

• Oral corticosteroid use unless prescribed as replacement therapy in the case ofadrenal insufficiency.

• Ongoing use of agents listed in locally approved prescribing information as causingimmunosuppression.

• Prior history of organ transplantation.

• Pregnancy or lactation.