Mechanism of Action Trial of ColoAd1 (MOA)

Akamis Bio

Status and phase: Completed; Phase 1

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

Treatments: Biological: Colo-Ad1

Study type: Interventional

Funder types: Industry

Identifiers

NCT02053220

ColoAd1-1002

Details and patient eligibility

About

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.

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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17 participants in 2 patient groups

Intra-tumoural cohort

Experimental group

Treatment:

Biological: Colo-Ad1

Intra-venous cohort

Experimental group

Treatment:

Biological: Colo-Ad1