Clinical Trials /

rRp450-Phase I Trial in Liver Metastases and Primary Liver Tumors

NCT01071941

Description:

The purpose of this research study is to determine the safety of rRp450 and the highest dose of this agent that can be given to people safely. We are also looking to see how well the body tolerates the study agent, how the agent is absorbed by the liver cancers, how quickly the agent is eliminated from the body, and what kind of anti-cancer effect it may have. rRp450 is a type of gene therapy and a form of the Herpes simplex virus 1 (or HSV). HSV is a virus that usually causes cold sores of the mouth. In extremely rare circumstances, this virus can cause severe infections, such as an infection of the brain. rRp450 was developed from an HSV and specially altered to target and kill cancer cells.

Related Conditions:
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: rRp450-Phase I Trial in Liver Metastases and Primary Liver Tumors
  • Official Title: rRp450-Phase I Trial in Liver Metastases and Primary Liver Tumors

Clinical Trial IDs

  • ORG STUDY ID: 09-042
  • SECONDARY ID: 5R21CA119600
  • NCT ID: NCT01071941

Conditions

  • Liver Metastases
  • Primary Liver Cancers

Interventions

DrugSynonymsArms
administration of rRp450 into the hepatic arteryrRp450Group 1

Purpose

The purpose of this research study is to determine the safety of rRp450 and the highest dose of this agent that can be given to people safely. We are also looking to see how well the body tolerates the study agent, how the agent is absorbed by the liver cancers, how quickly the agent is eliminated from the body, and what kind of anti-cancer effect it may have. rRp450 is a type of gene therapy and a form of the Herpes simplex virus 1 (or HSV). HSV is a virus that usually causes cold sores of the mouth. In extremely rare circumstances, this virus can cause severe infections, such as an infection of the brain. rRp450 was developed from an HSV and specially altered to target and kill cancer cells.

Detailed Description

      -  Since we are looking for the highest dose of the study agent that can be administered
           safely without severe or unmanageable side effects in participants that have liver
           tumors, not everyone who participates in this research study will receive the same dose
           of the study drug. The dose the participant receives will depend on the number of
           participants who have been enrolled in the study before and how well they tolerated
           their doses.

        -  Depending upon when the participant enrolls in this study, they will either receive a
           single injection of rRp450, or up to 4 weekly injections of rRp450. Participants in both
           groups will be monitored after the rRp450 injection in the hospital and in the clinic.
           As of July, 2013, because the first phase of the study has been completed, all
           participants from here forward will receive 4 weekly injections of rRp450

        -  For the rRp450 injection, we will insert a small tube into the artery that supplies
           blood to the liver. rRp450 will be injected into this tube so it goes directly to the
           liver. Another tube is inserted into the blood vessel that drains blood from the liver.
           We will use this tube to take blood samples to monitor how the body absorbs and breaks
           down rRp450.

        -  After the rRp450 injection, participants will be monitored closely for any side effects.
           Vital signs will be closely monitored before, during and after rRp450 injection. After
           the rRp450 injection, the tubes are removed.

        -  The following tests and procedures are done before the rRp450 injection: determination
           of overall health condition, performance status evaluation, review of current
           medications and any side effects, physical exam and vital signs.

        -  The following tests and procedures will be done during the injection of rRp450: vital
           signs, review of any side effects, research blood samples taken from a vein in your arm,
           and research blood samples taken from your liver vein.

        -  The following tests and procedures will be done after rRp450 injection: 1 Hour after;
           blood tests: 6 and 12 hours after; blood tests, vital signs, routine blood tests,
           samples of saliva and swabs of the skin of the penis or vaginal secretions (hour 12
           only): 24 hours after, Between days 4 to 7 and Between days 10 to 14; review of current
           medications and side effects, physical exam, vital signs, routine blood tests, swab
           samples of saliva, blood test to see if the body has produced antibodies against HSV-1
           (only on day 4 to 7 and only for participants enrolled in the single injection group).

        -  Liver and tumor biopsies will be performed about 6 days after the rRp450 injection.

        -  Participants will be asked to return to the clinic 2 weeks, 4 weeks, and every 3 months
           thereafter after their last injection of study medication.
    

Trial Arms

NameTypeDescriptionInterventions
Group 1ExperimentalThe first subjects will receive a single infusion of rRp450. Subsequent subjects will receive rRp450 as four doses administered every 1-2 weeks.
  • administration of rRp450 into the hepatic artery

Eligibility Criteria

        Inclusion Criteria:

          -  18 years of age or more and able to understand and sign a written informed consent
             form

          -  Histologically confirmed diagnosis of cancer with liver metastases, or histologically
             confirmed primary liver cancer (e.g. hepatocellular carcinoma, cholangiocarcinoma, or
             gallbladder carcinoma). Subjects may have extrahepatic spread of malignancy, except
             they may not have brain metastases. Subjects with a history of more than one invasive
             malignancy remain eligible for this study, but in these instances, a liver biopsy is
             required to document the histology of the liver tumor. An exception to this criterion
             is made for basal cell carcinoma.

          -  Subjects must have primary or metastatic liver malignancies which are surgically
             unresectable, and exhausted all standard therapeutic options

          -  Patients with hepatocellular carcinoma must have received sorafenib as one of the
             standard treatment options prior to being enrolled into the study

          -  No liver surgery (including radiofrequency ablation), chemotherapy (including
             bevacizumab), immunotherapy, or liver radiotherapy within 4 weeks of enrollment.

          -  ECOG performance status 0, 1 or 2 and life expectancy of greater than 12 weeks based
             on the investigator's clinical judgment.

          -  Serum hematology and chemistry test results as outlined in the protocol.

          -  Tumor volume occupies less than 50% of liver by volume as assessed by CT scan or MRI
             scan within 4 weeks of treatment

          -  Negative pregnancy test (serum or urine) in premenopausal women

          -  Prior exposure to HSV-1 as determined by blood test

        Exclusion Criteria:

          -  Clinical or pathological diagnosis of cirrhosis, hemachromatosis, or heptic fibrosis

          -  Ascites or complete occlusion of main portal vein

          -  Hepatitis C infection, chronic infection with hepatitis B, infection with HIV, or
             evidence of hepatic insufficiency

          -  Inability to practice contraception with condoms as prescribed by the protocol

          -  Active infection requiring treatment with systemic antibiotics or systemic anti-fungal
             agents

          -  Being treated with immunosuppressive agents such as systemic corticosteroids or
             cyclosporine

          -  Unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac
             arrhythmia, or need for antiarrythmic medication for which inability to take an oral
             preparation of regular medication for 48 hours would represent an unacceptable risk.

          -  Known existing uncontrolled coagulopathy, hemorrhagic disorder, or inability to
             discontinue coumadin or plavix for 5 days prior to each treatment (except for
             prophylaxis against portacath-associated thrombosis, which does not require cessation
             of therapy).

          -  History of seizures

          -  Allergy to acyclovir or inability to receive contract for CT and MRI scans

          -  Prior liver resection of greater than 2 anatomic segments as defined by Couinaud
             (subjects that have undergone prior liver wedge excisions or segmental resections are
             not excluded on this basis alone).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Evaluate the safety and tolerability of rRp450 administered into the hepatic artery as a single dose.
Time Frame:3 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Assess the relationship between systemic rRp450 levels and clinical toxicity.
Time Frame:3 years
Safety Issue:
Description:
Measure:Evaluate tumor biopsies for rRp450 replication, tumor response and immune cell infiltrates.
Time Frame:3 years
Safety Issue:
Description:
Measure:Correlate radiographic and pathologic assessments of tumor response.
Time Frame:3 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Kenneth K. Tanabe, MD

Trial Keywords

  • rRp450
  • Herpes virus
  • Gene therapy

Last Updated