- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01071941
rRp450-Phase I Trial in Liver Metastases and Primary Liver Tumors
March 25, 2024 updated by: Kenneth K. Tanabe, MD
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
15
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Massachusetts General Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1
The first subjects will receive a single infusion of rRp450.
Subsequent subjects will receive rRp450 as four doses administered every 1-2 weeks.
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Administration of rRp450 into the hepatic artery either as a single infusion, or as four infusions administered every one to two weeks.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Evaluate the safety and tolerability of rRp450 administered into the hepatic artery as a single dose.
Time Frame: 3 years
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3 years
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Evaluate the safety and tolerability of rRp450 administered into the hepatic artery as four doses administered every 1-2 weeks.
Time Frame: 3 years
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3 years
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Determine the dose-limiting toxicities and maximum dose of rRp450 that can be safely administered into the hepatic artery when administered weekly for four doses.
Time Frame: 3 years
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3 years
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Characterize rRp450 pharmacokinetics and viral shedding.
Time Frame: 3 years
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3 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Assess the relationship between systemic rRp450 levels and clinical toxicity.
Time Frame: 3 years
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3 years
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Evaluate tumor biopsies for rRp450 replication, tumor response and immune cell infiltrates.
Time Frame: 3 years
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3 years
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Correlate radiographic and pathologic assessments of tumor response.
Time Frame: 3 years
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3 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Kenneth K. Tanabe, MD, Massachusetts General Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2010
Primary Completion (Estimated)
July 1, 2026
Study Completion (Estimated)
July 1, 2026
Study Registration Dates
First Submitted
January 13, 2010
First Submitted That Met QC Criteria
February 18, 2010
First Posted (Estimated)
February 19, 2010
Study Record Updates
Last Update Posted (Actual)
March 26, 2024
Last Update Submitted That Met QC Criteria
March 25, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 09-042
- 5R21CA119600 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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