Liver MetastasesPhase 1NCT01071941
rRp450-Phase I Trial in Liver Metastases and Primary Liver Tumors
A Phase 1 study testing administration of rRp450 into the hepatic artery in people with Liver Metastases and Primary Liver Cancers, run by Kenneth K. Tanabe, MD at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Metastases, Primary Liver Cancers
- What is being tested?
- administration of rRp450 into the hepatic artery
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to Jun 2024
- 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
- 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.
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- 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
Who cannot join
- 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
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- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02115
About this study
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.
Read the 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.
- Conditions
- Liver Metastases, Primary Liver Cancers
- Being tested
- administration of rRp450 into the hepatic artery
- Keywords
- rRp450, Herpes virus, Gene therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
administration of rRp450 into the hepatic arteryBiological
Also called rRp450
Administration of rRp450 into the hepatic artery either as a single infusion, or as four infusions administered every one to two weeks.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | The first subjects will receive a single infusion of rRp450. Subsequent subjects will receive rRp450 as four doses administered every 1-2 weeks. Receives: Biological: administration of rRp450 into the hepatic artery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety and tolerability of rRp450 administered into the hepatic artery as a single dose.
Measured: 3 years
Evaluate the safety and tolerability of rRp450 administered into the hepatic artery as four doses administered every 1-2 weeks.
Measured: 3 years
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.
Measured: 3 years
Characterize rRp450 pharmacokinetics and viral shedding.
Measured: 3 years
Secondary outcomes (3)
Assess the relationship between systemic rRp450 levels and clinical toxicity.
Measured: 3 years
Evaluate tumor biopsies for rRp450 replication, tumor response and immune cell infiltrates.
Measured: 3 years
Correlate radiographic and pathologic assessments of tumor response.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2010 (estimated)
- Study startOct 2010
- Primary completionJun 2024
- Study completionJun 2024
Why it stopped: Inadequate funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kenneth K. Tanabe, MD
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Kenneth K. Tanabe, MD, Massachusetts General Hospital
- Investigators
- Kenneth K. Tanabe, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01071941
- Sponsor's protocol ID
- 09-042
- Other IDs
- 5R21CA119600
- Status last verified
- Jun 2024
- First submitted
- 13 Jan 2010
- Last updated
- 18 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- rRp450-Phase I Trial in Liver Metastases and Primary Liver Tumors
- ClinicalTrials.gov ID
- NCT01071941
- Acronym / sponsor ID
- 09-042
- Conditions
- Liver Metastases, Primary Liver Cancers
- Keywords
- rRp450, Herpes virus, Gene therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate funding
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Kenneth K. Tanabe, MDUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Oct 2010 (actual)
- Primary completion
- Jun 2024 (actual)
- Study completion
- Jun 2024 (actual)
- First posted
- 19 Feb 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Biological: administration of rRp450 into the hepatic arteryThe first subjects will receive a single infusion of rRp450. Subsequent subjects will receive rRp450 as four doses administered every 1-2 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| administration of rRp450 into the hepatic arteryAlso: rRp450Administration of rRp450 into the hepatic artery either as a single infusion, or as four infusions administered every one to two weeks. | Biological | Group 1 |
Primary outcome
Evaluate the safety and tolerability of rRp450 administered into the hepatic artery as a single dose.
Time frame: 3 years
Evaluate the safety and tolerability of rRp450 administered into the hepatic artery as four doses administered every 1-2 weeks.
Time frame: 3 years
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
Characterize rRp450 pharmacokinetics and viral shedding.
Time frame: 3 years
3 secondary outcomes
Assess the relationship between systemic rRp450 levels and clinical toxicity.
Time frame: 3 years
Evaluate tumor biopsies for rRp450 replication, tumor response and immune cell infiltrates.
Time frame: 3 years
Correlate radiographic and pathologic assessments of tumor response.
Time frame: 3 years
Results and safety
The study was stopped early (reason given: Inadequate funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth K. Tanabe, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing administration of rRp450 into the hepatic artery in people with Liver Metastases and Primary Liver Cancers, run by Kenneth K. Tanabe, MD 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 10 inclusion and 11 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: stopped early, as of the sponsor's last update on 18 Jun 2024. 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 was stopped early (reason given: Inadequate funding). Results are not available in the source record.
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?
Evaluate the safety and tolerability of rRp450 administered into the hepatic artery as a single dose. (time frame: 3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Jun 2024.