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AzTrials

Advanced Malignant Solid NeoplasmPhase 1NCT01628640

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

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta in people with Advanced Malignant Solid Neoplasm and Hepatocellular Carcinoma, run by Mayo Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Pharmacological Study and Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
3 Aug 2012to 19 Apr 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of recombinant vesicular stomatitis virus-expressing interferon-beta (VSV-IFN-beta) in patients with hepatocellular carcinoma (HCC) refractory or intolerant to sorafenib therapy and patients with advanced solid tumors with liver predominant locally advanced/metastatic treatment refractory disease. (Arm A) II. To determine the maximum tolerated dose (MTD) of VSV-IFN-beta in patients with advanced solid tumors with subcutaneous/cutaneous lesions. (Arm B)

SECONDARY OBJECTIVES:

  1. To estimate the tumor response rate, injected lesion (TNi) and distant lesion (TNd) necrosis rate (with TNi and TNd response defined as >= 30% increase in necrosis from baseline) and overall survival. (Arm A)

TERTIARY OBJECTIVES:

  1. To determine the pharmacokinetic (PK) profile of VSV-IFN-beta in patients with HCC by or advanced solid tumors with liver predominant disease or subcutaneous/cutaneous lesions by measurement of VSV-IFN-beta in blood by reverse transcriptase polymerase chain reaction (RT-PCR).

II. To characterize the pharmacodynamics (PD) of VSV-IFN-beta by way of measuring serum interferon-beta and also VSV-RT-PCR of VSV-IFN-beta listed above.

III. Assess CD8+ T cell (both general and VSV-hIFN-beta specific) and natural killer (NK) cell responses.

IV. Assess status of human interferon beta pathway pre/post therapy in tumor/normal liver tissue (status of IFN-beta, interferon stimulated gene factor 3 [ISGF3 complex constituting signal transducer and activator of transcription (STAT)1/2 and p48 (ISGF3 gamma)]).

  1. Assess phosphorylation of STAT1/2 post-therapy. VI. Evaluate transcription of interferon mediated genes (protein kinase R, the death receptor-tumor necrosis factor [TNF]-related apoptosis-inducing ligand [TRAIL], 2'-5' oligoadenylate/ribonucleic acid [RNA]se L proteins, heat shock proteins [Hsp 60/70/90], major histocompatibility class antigens and interferon regulatory factor [IRF]-7).

VII. Assess presence of VSV in tumor/normal liver subsequent to administration of VSV-human IFN-beta (hIFN- beta).

VIII. For HCC patients only, assess preliminary relationships between hepatitis C genotype (in those patients that are hepatitis C positive) and any evidence of anti-tumor efficacy.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 arms.

ARM A: 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.

ARM B: Patients with advanced solid tumor with subcutaneous/cutaneous lesions receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally in up to 5 lesions on day 1.

After completion of study treatment, patients are followed up every 4 weeks for 3 years.

Being tested
Laboratory Biomarker Analysis, Pharmacological Study, Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • Recombinant Vesicular Stomatitis Virus-expressing Interferon-betaBiological

    Also called Recombinant VSV-IFN-beta, VSV-hIFN-b

    Given intratumorally

Study groups in NCT01628640
Study groupRoleWhat they receive
Arm A (viral therapy in single tumor location)ExperimentalPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta
Arm B (viral therapy in multiple locations)ExperimentalPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

    Measured: Up to 3 years

  3. 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.

    Measured: 4 weeks

  4. 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.

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

  5. 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.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2012 (estimated)
  2. Study start3 Aug 2012
  3. Primary completion19 Apr 2019
  4. Study completion19 Apr 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01628640
Sponsor's protocol ID
MC1148
Other IDs
NCI-2012-00890, 11-007114, MC1148, 4781, P50CA210964, R01FD004781, DP2CA195764
Status last verified
Jul 2025
First submitted
23 Jun 2012
Last updated
3 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 36052732

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta in people with Advanced Malignant Solid Neoplasm and Hepatocellular Carcinoma, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 37 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01628640, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2025.

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