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

Phase 1
18 Years
Open (Enrolling)
Liver Metastases, Primary Liver Cancers

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Trial Information

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

- 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

- 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.

Inclusion Criteria:

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

- 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

- 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).

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Evaluate the safety and tolerability of rRp450 administered into the hepatic artery as a single dose.

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Kenneth K. Tanabe, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

October 2010

Completion Date:

May 2014

Related Keywords:

  • Liver Metastases
  • Primary Liver Cancers
  • rRp450
  • Herpes virus
  • Gene therapy
  • Liver Neoplasms
  • Neoplasm Metastasis
  • Neoplasms, Second Primary



Massachusetts General HospitalBoston, Massachusetts  02114-2617