Viral Therapy in Treating Patient With Refractory Liver Cancer or Advanced Solid Tumors

NCT01628640 | Completed Phase 1 DMC FDA Drug

• 7 other identifiers: MC1148NCI-2012-0089011-0071144781P50CA210964R01FD004781DP2CA195764
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the best dose and side effects of recombinant vesicular stomatitis virus expressing interferon beta in treating patients with liver cancer or solid tumors with lesions that have spread to other parts of the body and do not respond to treatment. The study virus has a gene inserted into it which will allow production of interferon beta, which is a substance that will restrict the spread of the virus to tumor cells and not healthy cells. It will also have some independent anti-cancer activity. Although the primary goal of this study is to evaluate the safety of delivery of this viral agent to people, patients may benefit clinically by having shrinkage or stabilization of their tumor or reduction in their cancer related symptoms (e.g., pain). Funding Source - FDA OOPD.

Conditions

Advanced Malignant Solid Neoplasm; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (5)

• Best tumor response, defined as the best objective status recorded among patients with measurable disease at baseline using Response Evaluation Criteria in Solid Tumors version 1.1

  Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall, by dose level, and by disease type). Examined in an exploratory and hypothesis-generating fashion.

  From the start of the treatment until disease progression, assessed up to 3 years

• Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  All eligible patients that have initiated treatment will be considered evaluable for assessing adverse event rate(s). The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed by dose level to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Examined in an exploratory and hypothesis-generating fashion.

  Up to 3 years

• Maximum tolerated dose, defined as the highest dose at which no more than 1/6 patients experiences dose limiting toxicities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Dose limiting toxicities defined as an adverse event during the first 4 weeks following injection. A modified "3+3" Fibonacci dose escalation scheme will be used Examined in an exploratory and hypothesis-generating fashion.

  4 weeks

• Overall survival

  The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type). Examined in an exploratory and hypothesis-generating fashion.

  From registration to death due to any cause, assessed up to 3 years

• Tumor necrosis

  Injected lesion and distant lesion necrosis rate will be defined as injected lesion and distant lesion \>= 30% increase in necrosis from baseline, respectively. Frequency and relative frequency will be computed for each (overall, by dose level and by disease type). This analysis will be conducted in hepatocellular carcinoma patients only.

  Up to 3 years

Study Arms (2)

Arm A (viral therapy in single tumor location)

EXPERIMENTAL

Patients with hepatocellular carcinoma or advanced solid tumor with liver lesions receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally in a single tumor location on day 1.

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta

Arm B (viral therapy in multiple locations)

EXPERIMENTAL

Patients with advanced solid tumor with subcutaneous/cutaneous lesions receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally in up to 5 cutaneous, subcutaneous, or soft tissue tumor lesions on day 1.

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (viral therapy in single tumor location); Arm B (viral therapy in multiple locations)

Pharmacological Study OTHER

Correlative studies

Arm A (viral therapy in single tumor location); Arm B (viral therapy in multiple locations)

Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta BIOLOGICAL

Given intratumorally

Also known as: Recombinant VSV-IFN-beta, VSV-hIFN-b

Arm A (viral therapy in single tumor location); Arm B (viral therapy in multiple locations)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ARM A: Histologically or cytologically confirmed hepatocellular carcinoma that is refractory (by Response Evaluation Criteria in Solid Tumors \[RECIST\] or modified \[m\]RECIST criteria or with unequivocal clinical progression of disease) to or intolerant (defined as inability to administer further sorafenib due to drug related toxicities) of sorafenib based therapy or advanced solid tumor with liver predominant disease burden that has progressed on or is intolerant to standard
• ARM A: Absolute neutrophil count (ANC) \>= 1000/mm\^3
• ARM A: Platelet count \>= 80,000/mm\^3
• ARM A: Hemoglobin \>= 10 g/dl
• ARM A: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 5 x ULN
• ARM A: Creatinine =\< 1.5 x ULN
• ARM A: Total bilirubin =\< 1.5 x ULN
• ARM A: International normalized ratio (INR) =\< 1.5 x ULN
• ARM A: Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN
• ARM A: Ability to provide informed written consent
• ARM A: Willingness to return to Mayo Clinic in Arizona for follow-up
• ARM A: Life expectancy \>= 12 weeks
• ARM A: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• ARM A: Willingness to provide all biological specimens as required by the protocol
• ARM A: Negative serum pregnancy test =\< 7 days prior to registration for women of childbearing potential only

You may not qualify if:

• ARM A: Uncontrolled infection
• ARM A: Systemic anti-cancer therapy =\< 4 weeks prior to registration
• ARM A: Known human immunodeficiency virus (HIV) infection
• ARM A: Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy
• ARM A: Pregnant or nursing women
• ARM A: History of bone marrow or solid organ transplantation
• ARM A: Patient for whom surgical resection or liver transplantation would be more appropriate
• ARM A: Any condition, which in the opinion of the investigator would render the patient unsuitable to participate in the study
• ARM A: Any corticosteroid use =\< 28 days prior to registration
• ARM A: Any radioembolization or transarterial chemoembolization (TACE) =\< 84 days prior to registration
• ARM B: Uncontrolled infection
• ARM B: Systemic anti-cancer therapy =\< 4 weeks prior to registration
• ARM B: Known HIV infection
• ARM B: Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy
• ARM B: Pregnant or nursing women

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Related Publications (1)

• Nagalo BM, Zhou Y, Loeuillard EJ, Dumbauld C, Barro O, Elliott NM, Baker AT, Arora M, Bogenberger JM, Meurice N, Petit J, Uson PLS Jr, Aslam F, Raupach E, Gabere M, Basnakian A, Simoes CC, Cannon MJ, Post SR, Buetow K, Chamcheu JC, Barrett MT, Duda DG, Jacobs B, Vile R, Barry MA, Roberts LR, Ilyas S, Borad MJ. Characterization of Morreton virus as an oncolytic virotherapy platform for liver cancers. Hepatology. 2023 Jun 1;77(6):1943-1957. doi: 10.1002/hep.32769. Epub 2022 Oct 11.

  PMID: 36052732 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Mitesh J. Borad, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2012
• First Posted: June 27, 2012
• Study Start: August 3, 2012
• Primary Completion: April 19, 2019
• Study Completion: April 19, 2019
• Last Updated: July 3, 2025

Record last verified: 2025-07

Locations

US (1)