mechanism of action trial of coload1

Conditions: Resectable Colon Cancer; Resectable Non-small Cell Lung Cancer; Resectable Bladder Cancer; Resectable Renal Cell Carcinoma

Summary: to assess the pattern of coload1 viral delivery and viral expression within colon tumour tissue when administered by intra-tumoural injection or within colon, non-small cell lung, bladder and renal cell tumour tissues following coload1 administration by intravenous infusion.


Eligibility criteria:
inclusion criteria: patients must meet all the following criteria to be eligible for participation: * able and willing to provide written informed consent and to comply with the study protocol * age ≥ 18 years * patients with histologically confirmed resectable colon cancer, nsclc (squamous and non-squamous), bladder cancer (urothelial cell carcinoma) or rcc (renal cell carcinoma), scheduled for resection of primary tumour and with planned resection of draining lymph nodes for colon cancer * diagnostic colonoscopy performed at the study centre (cohorts a and b only) or a referral centre (cohort b only) and a report from this colonoscopy available for the study * tumour size of 3 cm or more in diameter as estimated during diagnostic colonoscopy for cohorts a and b or by ct-scan for cohorts c, d and e. * at least 2 weeks since the last dose of any intravenous systemic chemotherapy at time of first administration of coload1 * recovered to grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies. * able to undergo surgery with general anaesthesia * surgery planned and administration of coload1 feasible within * 15 days of planned surgery (following it administration or following first dose of iv administration) for cohorts a and b * 10 - 25 days of first coload1 administration for cohorts c, d and e * ecog performance status score of 0 or 1 * adequate renal function * creatinine ≤ 1.5 mg/dl or calculated creatinine clearance using the cockcroft-gault formula ≥ 60 ml/min, or measured creatinine clearance ≥60 ml/min, * absence of clinically significant haematuria on urinalysis: dipstick \< 2+ * absence of clinically significant proteinuria on urinalysis: dipstick \< 2+. * adequate hepatic function * serum bilirubin \<1.5 x uln * ast and alt ≤ 3 x uln * adequate bone marrow function: * anc ≥ 1.5 x 109/l, * platelets ≥ 100 x 109/l, * haemoglobin ≥ 90 g/l * adequate coagulation tests: inr ≤ 1.5 x uln; * for females of childbearing potential (defined as \<2 years after last menstruation or not surgically sterile), a negative pregnancy test must be documented prior to enrolment; * for women who are not postmenopausal (24 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use two adequate methods of contraception, including at least one method with a failure rate of \< 1% per year (e.g., hormonal implants, combined oral contraceptives, vasectomized partner), during the treatment period and for at least 3 months after the last dose of study drug; * for men: agreement to use a barrier method of contraception during the treatment period and for at least 6 months after the last dose of study drug exclusion criteria for all patients: patients who meet any of the following criteria are not eligible for enrolment: * rectal tumours; (cohorts a and b); * an obstructive tumour of the intestine (cohorts a and b only) or of the urinary tract (cohort d); * any condition necessitating surgery in less than 8 days (cohorts a or b) or 10 days (cohorts c, d or e); * pregnant or lactating (nursing) women; * known and/or a history or evidence of significant immunodeficiency due to underlying illness (e.g. hiv/aids) and/or medication (e.g. systemic corticosteroids at doses higher than dexamethasone 10 mg or equivalent, or other immunosuppressive medications including cyclosporine, azathioprine, interferons, within the past 4 weeks); * splenectomy * prior allogeneic or autologous bone marrow or organ transplantation * active infections requiring antibiotics, physician monitoring, or recurrent fevers \>38.0 degrees centigrade associated with a clinical diagnosis of active infection * active viral disease, positive serology for hiv, hepatitis b or hepatitis c * use of the following anti-viral agents: * ribavirin, adefovir, lamivudine or cidofovir within 7 days prior to day 1; * or peg-ifn (within 14 days prior to day 1); * administration of an investigational drug within 28 days prior to first dose of coload1 * major surgery within 4 weeks or radiotherapy within 3 weeks prior to first dose of coload1 * another primary malignancy within the past 3 years (except for non-melanoma skin cancer or cervical cancer in situ) * known cns metastasis * inflammatory diseases of the bowel (cohorts a and b only) or any inflammatory disease that may require treatment with corticosteroids. * any condition or illness that, in the opinion of the investigator or the medical monitor, would compromise patient safety or interfere with the evaluation of the safety of the drug * known allergy to treatment medication or its excipients * any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent.