This research is being done because these viruses have been shown to shrink tumours in animals and human tumour samples by selectively killing cancer cells and creating an immune response to the tumour antigen contained in the viruses. This effect has been shown to increase when the AdMA3 virus is given first. It is not clear if this treatment will offer better results than standard treatment.
The purpose of the first phase of this study (phase I) is to find the dose of a new therapy, the MG1 Maraba/MAGE-A3 (MG1MA3) virus that can be given alone and in combination with the Adenovirus/MAGE-A3 (AdMA3) virus. In the first part of the study, patients may receive the Maraba virus, the Adenovirus or both viruses. To identify the highest safe dose of the Maraba virus alone or in combination the study will start at a dose lower than the one that does not cause side effects in animals. Participants are given one or both of these therapies and are watched very closely to see what side effects they have and to make sure the side effects are not severe. If serious side effects are seen in patients at the first dose level, doses of MG1MA3 may be lowered in subsequent patients. If the side effects are not serious, then more potential participants are asked to join this study and are given higher doses. This will continue until the maximum feasible dose level is reached or one of the lower doses is found that causes serious but temporary side effects. Doses higher than that will not be given.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
56
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada
Ottawa Hospital Research Institute
Ottawa, Ontario, Canada
University Health Network
Toronto, Ontario, Canada
Phase I: Toxicity as measured by adverse events
To Determine maximum feasible dose (MFD) of: * MG1MA3 when administered alone on day 1 \& day 4 (Arm A) * MG1MA3 when administered on day 1 \& 4 or days 1, 4, 8 \&11 following immunologic priming with AdMA3 (Arm C) * To confirm the safety profile of AdMA3 administration (Arm B).
Time frame: 3 years
Phase II: Objective tumour response rate (ORR) using RECIST v1.1.
To evaluate the objective tumour response rate (ORR) using RECIST v1.1.
Time frame: 16 weeks
Phase I: Number and Severity of Adverse Events in patients
To determine the safety profile of: * MG1MA3 when administered alone (Arm A); * MG1MA3 when administered on day 1 \& 4 or days 1, 4, 8 \&11 following immunologic priming with AdMA3 (Arm C). Adverse events will be monitored on an ongoing basis by the central office and their frequencies reported semi-annually at investigators' meetings. Toxic effects will be categorized using the CTCAE. The worst event for each patient in each category or subcategory will be described. Both events related and unrelated to treatment will be captured.
Time frame: 8 weeks
Phase I: MG1MA3 clearance and secondary replication from pharmacokinetics and viral shedding
To determine the pharmacokinetics, including viral shedding, of MG1MA3 when administered: * Alone on day 1 \& day 4 (Arm A); * Following immunologic priming with AdMA3 (Arm C). Pharmacokinetic parameters including MG1MA3 clearance and secondary replication (genomes and infectious units), will be evaluated in blood over time and summarized descriptively by treatment arms in phase I portion.
Time frame: 3 years
Phase I: Delivery to, and viral detection and replication within, tumours for MG1MA3
To determine the delivery to, and viral detection and replication within, tumours for MG1MA3 when administered: * Alone on day 1 \& day 4 (Arm A); * Following immunologic priming with AdMA3 (Arm C).
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Time frame: 3 years
Phase I: Cellular and humoral immune response to virus and tumour antigens
To determine the cellular and humoral immune response to virus and tumour antigens (for all arms).
Time frame: 3 years
Phase I: Efficacy using RECIST v1.1 and iRECIST
To evaluate preliminary evidence of efficacy using RECIST v1.1 and iRECIST
Time frame: 3 years
Phase II: pharmacokinetics (PK) of MG1MA3 (MG1MA3 clearance and secondary replication (genomes and infectious units)
To further explore the pharmacokinetics (PK) of MG1MA3. Pharmacokinetic parameters including MG1MA3 clearance and secondary replication (genomes and infectious units), will be evaluated in blood over time and summarized descriptively by tumour types in phase II portion.
Time frame: 3 years
Phase II: cellular and humoral immune response to virus and tumour antigens
To further evaluate the cellular and humoral immune response to virus and tumour antigens.
Time frame: 16 weeks
Phase II: toxicity as measured by adverse events of MG1MA3 following AdMA3
To further explore the safety profile of MG1MA3 following AdMA3
Time frame: 3 years
Phase II: Response by iRECIST
To evaluate response by iRECIST
Time frame: 16 weeks