Mechanism of Action Trial of ColoAd1 (MOA)

This is an interventional treatment trial for Resectable Colon Cancer Read More

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.