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

NCT01071941 | Terminated Phase 1 DMC

• 2 other identifiers: 09-0425R21CA119600
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Liver Metastases; Primary Liver Cancers

Keywords

rRp450; Herpes virus; Gene therapy

Outcome Measures

Primary Outcomes (4)

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

  3 years

• Evaluate the safety and tolerability of rRp450 administered into the hepatic artery as four doses administered every 1-2 weeks.

  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.

  3 years

• Characterize rRp450 pharmacokinetics and viral shedding.

  3 years

Secondary Outcomes (3)

• Assess the relationship between systemic rRp450 levels and clinical toxicity.

  3 years

• Evaluate tumor biopsies for rRp450 replication, tumor response and immune cell infiltrates.

  3 years

• Correlate radiographic and pathologic assessments of tumor response.

  3 years

Study Arms (1)

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.

Biological: administration of rRp450 into the hepatic artery

Interventions

administration of rRp450 into the hepatic artery BIOLOGICAL

Administration of rRp450 into the hepatic artery either as a single infusion, or as four infusions administered every one to two weeks.

Also known as: rRp450

Group 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Kenneth K. Tanabe, MD: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Study Officials

• Kenneth K. Tanabe, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Surgical Oncology

Study Record Dates

• First Submitted: January 13, 2010
• First Posted: February 19, 2010
• Study Start: October 1, 2010
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: June 18, 2024

Record last verified: 2024-06

Locations

US (1)