Clinical trial NCT02053220: Mechanism of Action Trial of ColoAd1
Official title: A Phase 1 Clinical Study of Intra-tumoural Injection or Intravenous Infusion of a Group B Oncolytic Adenovirus (ColoAd1) in Patients With Cancer Who Are Candidates for Resection of Primary Tumour
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Resectable Colon Cancer
Resectable Non-small Cell Lung Cancer
Resectable Bladder Cancer
Resectable Renal Cell Carcinoma
Lead sponsor: Akamis Bio
Sponsor class: INDUSTRY
First posted: 2014-02-03
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Composite measure of viral delivery and spread
timeFrame: Up to Day 25
Secondary outcomes:
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro CIOCC
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocío
Study officials:
References:
citation: Garcia-Carbonero R, Salazar R, Duran I, Osman-Garcia I, Paz-Ares L, Bozada JM, Boni V, Blanc C, Seymour L, Beadle J, Alvis S, Champion B, Calvo E, Fisher K. Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection. J Immunother Cancer. 2017 Sep 19;5(1):71. doi: 10.1186/s40425-017-0277-7.