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

This study has suspended participant recruitment.
(Grade 5 event, protocol modification pending)
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01628640
First received: June 23, 2012
Last updated: July 6, 2017
Last verified: December 2016
  Purpose
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.

Condition Intervention Phase
Advanced Malignant Solid Neoplasm Hepatocellular Carcinoma Other: Laboratory Biomarker Analysis Other: Pharmacological Study Biological: Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase I Trial of Intratumoral Injection of Vesicular Stomatitis Virus Expressing Human Interferon Beta in Patients With Sorafenib Refractory/Intolerant Hepatocellular Carcinoma, Advanced Solid Tumors With Liver Predominant Locally Advanced/Metastatic Disease or Subcutaneous/Cutaneous Lesions

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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 [ Time Frame: From the start of the treatment until disease progression, assessed up to 3 years ]
    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.

  • Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 3 years ]
    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.

  • 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 [ Time Frame: 4 weeks ]
    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.

  • Overall survival [ Time Frame: From registration to death due to any cause, assessed up to 3 years ]
    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.

  • Tumor necrosis [ Time Frame: Up to 3 years ]
    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.


Estimated Enrollment: 110
Actual Study Start Date: August 15, 2012
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (viral therapy in single tumor location)
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
Correlative studies
Other: Pharmacological Study
Correlative studies
Biological: Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta
Given intratumorally
Other Names:
  • Recombinant VSV-IFN-beta
  • VSV-hIFN-b
Experimental: Arm B (viral therapy in multiple locations)
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
Correlative studies
Other: Pharmacological Study
Correlative studies
Biological: Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta
Given intratumorally
Other Names:
  • Recombinant VSV-IFN-beta
  • VSV-hIFN-b

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • ARM A: Child Pugh Score A or B7 (patients with ascites must have paracentesis performed within scope of standard of care, to be able to successfully perform intratumoral injection procedure)
  • ARM A: The patient and their partner agree to use a barrier method of contraception during the study and 4 months following end of active treatment
  • ARM A: Disease burden in liver not affecting more than 25% of liver
  • ARM A: Predominant intrahepatic burden (> 75%) of disease (i.e. patients with widespread extrahepatic disease to organs other than the liver will not be included)
  • ARM B: Histologically or cytologically confirmed solid tumor with subcutaneous/cutaneous lesions that is refractory (RECIST or with unequivocal clinical progression of disease) to or intolerant to standard therapy
  • ARM B: Absolute neutrophil count (ANC) >= 1000/mm^3
  • ARM B: Platelet count >= 100,000/mm^3
  • ARM B: Hemoglobin >= 10 g/dl
  • ARM B: AST/ALT =< 2.5 x ULN
  • ARM B: Creatinine =< 1.5 x ULN
  • ARM B: Total bilirubin =< 1.5 x ULN
  • ARM B: INR =< 1.5 x ULN
  • ARM B: aPTT =< 1.5 x ULN
  • ARM B: Ability to provide informed written consent
  • ARM B: Willingness to return to Mayo Clinic in Arizona for follow-up
  • ARM B: Life expectancy >= 12 weeks
  • ARM B: ECOG performance status (PS) 0 or 1
  • ARM B: Willingness to provide all biological specimens as required by the protocol
  • ARM B: Negative serum pregnancy test =< 7 days prior to registration for women of childbearing potential only
  • ARM B: Child Pugh Score A
  • ARM B: The patient and their partner agree to use a barrier method of contraception during the study and 4 months following end of active treatment
  • ARM B: Disease burden in liver not affecting more than 25% of liver

Exclusion Criteria:

  • 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
  • ARM B: History of bone marrow or solid organ transplantation
  • ARM B: Patient for whom surgical resection or liver transplantation would be more appropriate
  • ARM B: Any condition, which in the opinion of the investigator would render the patient unsuitable to participate in the study
  • ARM B: Any corticosteroid use =< 28 days prior to registration
  • ARM B: Any radioembolization or TACE =< 84 days prior to registration
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01628640

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mitesh Borad Mayo Clinic
  More Information

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01628640     History of Changes
Other Study ID Numbers: MC1148
NCI-2012-00890 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
11-007114
MC1148 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
4781 ( Other Grant/Funding Number: OPD Grant )
Study First Received: June 23, 2012
Last Updated: July 6, 2017

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Interferons
Interferon-beta
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 21, 2017