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About
This study is an open-label study. It has two stages. Stage 1 is a dose escalation phase of the study to determine and evaluate the safety and tolerability of repeated treatments with a genetically engineered herpes simplex virus NV1020 administered locoregionally to the liver.
Stage 2 is to evaluate the dose found in Stage 1 to be "optimally tolerated". Stage 2 is to assess the efficacy of the optimally tolerated dose of NV1020 by itself and in combination with second-line chemotherapy.
Assignment to Stage 1 or Stage 2 of the study is determined by when the patient enters the study.
Full description
This study is designed to evaluate the effects of repeated treatments with NV1020, prior to second-line chemotherapy, and to determine an appropriate dose level of NV1020 in a multiple dose regimen for later Phase II studies.
Sequential, open-label cohort dose escalation of NV1020 (stage 1) followed by an expansion of one selected dose cohort (stage 2).
Study results will be reviewed periodically by an independent DSMB who will approve each cohort dose escalation.
During the dose escalation stage, 3 cohorts of patients (3 in each) will be treated with 4 fixed doses of NV1020, with the dose level increasing for successive cohorts. A patient will be observed for a minimum of 7 days after the first NV1020 infusion before the next patient in the same cohort is given NV1020. The first patient in the next higher dose cohort will receive NV1020 no earlier than 14 days after the last patient in the prior cohort has finished NV1020 infusions. One additional cohort (half log higher increment) may be approved by the DSMB, if considered necessary to define MTD. Dose-limiting toxicity will be determined using NCI CTC criteria and a suitable dose level for later evaluation will be selected.
In the second stage of the study, the dose cohort considered to show the best therapeutic index will be expanded by the addition of 18 further patients. For all patients in this study, investigational treatment with NV1020 will be followed by a minimum of two cycles of second-line therapy using anti-neoplastic drugs approved by the FDA for colorectal cancer and selected by the investigator.
All patients will be followed up periodically until death. Permission for autopsy will be sought.
Enrollment
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Inclusion criteria
Exclusion criteria
Dominant extrahepatic disease, including cerebral metastases, significant malignant ascites or other extrahepatic metastases that are symptomatic, in critical locations or otherwise likely to confound NV1020 evaluations, in the opinion of the investigator
Seronegative for HSV-1
Significant active/unstable non-malignant disease or laboratory test (hematology and chemistry) results that meet any of the following:
Chemotherapy < 4 weeks prior to the first NV1020 infusion (mitomycin or nitrosurea < 6 weeks)
Immunotherapy < 6 weeks prior to the first NV1020 infusion
Radiotherapy (external or internal) to the liver
Major surgery (excluding pump placement and cholecystectomy) ≤ 2 weeks prior to the first NV1020 infusion but the subject must be clinically stable. Pump placement and cholecystectomy ≤ 1 week prior to the first NV1020 infusion but the subject must be clinically stable
Female who is pregnant or nursing
Patients wishing to conceive within 2 months after the last infusion of NV1020
Any investigational agent administered less than or equal to 4 weeks prior to NV1020 infusion
Acute HSV infection requiring systemic antiviral therapy or history of serious HSV infection (e.g., ocular, encephalitic, etc.)
Active viral hepatitis (evidence for infection with hepatitis A, B or C viruses)
Known infection with HIV
Known hypersensitivity to any component of the NV1020 formulation
History of, or current, bleeding or coagulation disorder
History of significant hepatic fibrosis, cirrhosis, or hemachromatosis
History of malignancy other than colorectal cancer, within 5 years prior to start of study participation, with the exception of in situ cervical or skin carcinoma
Active severe infection and any other concurrent disease or medical conditions that are likely to interfere with the study, as judged by the investigator
Systemic corticosteroid administration < 4 weeks prior to starting NV1020 treatment
Prior treatment with NV1020 or other putative oncolytic viruses
Primary purpose
Allocation
Interventional model
Masking
32 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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