metastatic colorectal cancer MedDRA version: 14.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: ColoAd1
Pharmaceutical Form: Concentrate for solution for injection
Current Sponsor code: ColoAd1
Other descriptive name: a live replicating group B chimeric oncolytic adenovirus
Concent
Sponsors
Psioxus Therapeutics Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: INCLUSION CRITERIA FOR ALL PATIENTS 1 Patients must provide written informed consent 2 Age ? 18 years and the patient must be at least the legal age limit to be able to give consent within the jurisdiction the study is taking place. 3 ECOG performance status 0 or 1 (See Appendix 1) 4 Predicted life expectancy of 3 months or more 5 Ability to comply with study procedures in the Investigator?s opinion 6 Recovered to Grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies. 7 Adequate renal, hepatic and bone marrow functions 8 At least 3 weeks since the last dose of any intravenous systemic chemotherapy and at least two weeks since the last oral dose of capecitabine at time of first administration of ColoAd1. For Phase 1 Dose-escalation stage only: Solid tumour of epithelial origin not responding to standard therapy or for whom no standard treatment exists For Phase 1 Dose Expansion Stage only: 1. Metastatic colorectal carcinoma not responding to standard therapy, 2. ? 3 prior lines of systemic therapy for advanced disease; For Phase 2: 1. Metastatic colorectal cancer; 2. Have received 3 - 4 months of first line chemotherapy with either FOLFOX, FOLFIRI or CAPOX, with or without bevacizumab; 3. At least one measurable lesion according to RECIST 1.1 criteria; 4. Documented partial response or stable disease; 5. Eligible to receive chemotherapy with FOLFOX or CAPOX +/- bevacizumab after a short chemotherapy interruption (3-4 weeks), time to administer ColoAd1; Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 99 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
Exclusion criteria: For all patients: Pregnant or breast feeding females; Known history or evidence of significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids, 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 or known 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 first administration of ColoAd1); 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); CNS metastasis that is symptomatic and/or requires treatment; 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. For Phase 2 patients: Progression on first line therapy; A complete response on first line therapy; Use of first line therapy for longer than 4 months; Use of any first line treatment with a chemotherapy regimen other than FOLFOX, FOLFIRI or CAPOX (with or without bevacizumab). More than 6 weeks since the last administration of 5 FU, capecitabine, oxaliplatin or irinotecan. Household contact: Pregnant or breast feeding females; Children < 1 year old; A household contact with significant immunodeficiency due to underlying illness (e.g.HIV/AIDS) and/or medication (e.g. systemic corticosteroids).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: - To evaluate the safety and tolerability of ColoAd1, when administered by sub-acute fractionated IV injection to patients with advanced or metastatic epithelial solid tumours not responding to standard therapy or for whom no standard treatment exists - To determine the maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of ColoAd1 when administered by sub-acute fractionated intravenous (IV) injection to patients with advanced or metastatic epithelial solid tumours not responding to standard therapy or for whom no standard treatment exists, and to recommend a dose for phase II studies. Phase II: - To evaluate the progression free survival (PFS) in patients with metastatic colorectal cancer, who receive ColoAd1 administered by sub-acute fractionated IV injection as an intensification of first line chemotherapy compared with first line chemotherapy alone.;Secondary Objective: Phase I - To examine the anti-tumour activity of ColoAd1 administered by sub-acute fractionated IV injection in patients with advanced or metastatic solid tumours of epithelial origin not responding to standard therapy or for whom no standard therapy exists, as measured by response rate, duration of response , clinical benefit rate, progression free survival and overall survival. - To assess the kinetics and clearance of ColoAd 1 from the circulation; - To assess the potential for ColoAd1 shedding (phase I Dose Escalation only); - To measure ColoAd1 specific neutralizing antibody levels Phase II - To evaluate the dose, safety and tolerability of ColoAd1 when administered by sub-acute fractionated IV injection in sequence with chemotherapy for the first line treatment of metastatic colorectal cancer - To further examine the anti-tumour activity of ColoAd1;Primary end point(s): Phase 1: Safety and tolerability Determine a maximum tolerated dose (MTD) / maximum feasible dose (MFD) of ColoAd1 when administered by sub-acute fractionated IV injection (pha | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I - Response rate defined by RECIST v1.1 - Duration of response defined by RECIST v1.1 - Clinical benefit (CB) rate i.e. complete response (CR) + partial response (PR) + stable disease (SD) ?12 weeks defined by RECIST v1.1 - Progression-Free Survival, defined as the number of days from date of randomization to date of documented clinical/radiological progression or date of death, whichever is earlier. - Overall survival defined as the time from first dose of ColoAd1 to death due to any cause. - Kinetics and clearance of ColoAd 1 from the circulation (phase I Dose Escalation only) - ColoAd1 shedding (phase I Dose Escalation only); Phase II - Safety and tolerability - Progression-Free Survival, defined as the number of days from date of randomization to date of documented clinical/radiological progression or date of death, whichever is earlier. - Response rate according to RECIST 1.1 criteria - Response rate according to Choi?s criteria - Duration of response defined by RECIST v1.1 - Clinical benefit (CB) rate i.e. complete response (CR) + partial response (PR) + stable disease (SD) ?12 weeks defined by RECIST v1.1 - Overall survival defined as the time from first dose of ColoAd1 to death due to any cause.;Timepoint(s) of evaluation of this end point: 61 days/ 120 days | — |
Countries
Belgium, Spain, United Kingdom
Contacts
Public ContactProject Manager
INC Research
Outcome results
None listed