Safety and Efficacy of a Genetically Engineered Herpes Simplex Virus NV1020 to Treat Colorectal Cancer Metastatic to Liver

This study has been completed.
Sponsor:
Information provided by:
MediGene
ClinicalTrials.gov Identifier:
NCT00149396
First received: September 6, 2005
Last updated: December 12, 2008
Last verified: December 2008
  Purpose

This study is an open-label study. It has two stages. Stage 1 is a dose escalation phase of the study to determine and evaluate the safety and tolerability of repeated treatments with a genetically engineered herpes simplex virus NV1020 administered locoregionally to the liver.

Stage 2 is to evaluate the dose found in Stage 1 to be "optimally tolerated". Stage 2 is to assess the efficacy of the optimally tolerated dose of NV1020 by itself and in combination with second-line chemotherapy.

Assignment to Stage 1 or Stage 2 of the study is determined by when the patient enters the study.


Condition Intervention Phase
Colorectal Cancer
Liver Neoplasms
Drug: NV1020
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-Label Study (With a Sequential Dose Escalation Stage Followed by an Expansion of a Selected Dose Cohort), to Evaluate the Safety and Anti-Tumor Effects of NV1020 Administered Repeatedly Via Hepatic Artery Infusion Prior to Second-Line Chemotherapy, in Patients With Colorectal Adenocarcinoma Metastatic to the Liver

Resource links provided by NLM:


Further study details as provided by MediGene:

Primary Outcome Measures:
  • Incidence of adverse events and dose limiting adverse events [ Time Frame: Last patient out ] [ Designated as safety issue: Yes ]
  • Clinical laboratory safety results [ Time Frame: Last patient out ] [ Designated as safety issue: Yes ]
  • NV1020 pharmacokinetics-presence of NV1020 in body fluids/skin [ Time Frame: Last patient out ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor response after administration of NV1020 followed by a minimum of 2 cycles of chemotherapy, determined by radiological (computed tomography [CT] scan) assessment of liver size and positron emission tomography (PET) scan [ Time Frame: Last patient out ] [ Designated as safety issue: No ]
  • Mean change from baseline in serum carcinoembryonic antigen (CEA) after administration of NV1020 and 2 cycles of chemotherapy [ Time Frame: Last patient out ] [ Designated as safety issue: No ]
  • Pharmacodynamic effects of NV1020 (NV1020 neutralizing antibody titer assay, cytokines, CEA) [ Time Frame: Last patient out ] [ Designated as safety issue: No ]
  • Time to disease progression; Survival time [ Time Frame: Withdrawal or death of last patient ] [ Designated as safety issue: No ]

Estimated Enrollment: 27
Study Start Date: July 2004
Study Completion Date: December 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: NV1020
    NV1020 dose levels: 3x10E6, 1x10E7, and 3x10E7 plaque forming units, administered via hepatic artery infusion, over 10 minutes and repeated every 1-2 weeks for 4-8 weeks
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Ability to understand and willingness to sign a written informed consent (includes willingness to avoid physical intimacy during and for 2 weeks post NV1020 treatment)
  2. 18 years or more of age
  3. Colorectal adenocarcinoma histologically confirmed within one year prior to enrollment in the study
  4. Liver dominant metastases (CT-measurable lesions with less than 50% total liver involvement), histologically confirmed
  5. Failed conventional chemotherapy for metastatic disease
  6. Candidate for additional chemotherapy
  7. Karnofsky Performance Status 70% or greater
  8. Life expectancy greater than or equal to 4 months, based on the investigator's opinion
  9. Seropositive for herpes simplex virus-1 (HSV-1)
  10. Fecund females: negative for pregnancy test (urine or serum)
  11. Effective double-barrier contraception for a minimum of 2 months following final infusion of NV1020

Exclusion Criteria:

  1. Dominant extrahepatic disease, including cerebral metastases, significant malignant ascites or other extrahepatic metastases that are symptomatic, in critical locations or otherwise likely to confound NV1020 evaluations, in the opinion of the investigator
  2. Seronegative for HSV-1
  3. Significant active/unstable non-malignant disease or laboratory test (hematology and chemistry) results that meet any of the following:

    • White blood cell count (WBC) less than or equal to 3 x 10e3/mm3
    • Absolute neutrophil count (ANC) less than or equal to 1.5 x 10e3/mm3
    • Platelets less than or equal to 100,000/mm3
    • Hemoglobin (Hgb) less than or equal to 9.0 g/dL
    • Prothrombin time/partial thromboplastin time (PT/PTT) > upper limit of normal (ULN)
    • Serum creatinine > 2.0 mg/dL
    • AST or ALT > 2.5 times ULN or total bilirubin > 1.5 times ULN
    • Alkaline phosphatase > 2.5 times ULN
  4. Chemotherapy < 4 weeks prior to the first NV1020 infusion (mitomycin or nitrosurea < 6 weeks)
  5. Immunotherapy < 6 weeks prior to the first NV1020 infusion
  6. Radiotherapy (external or internal) to the liver
  7. Major surgery (excluding pump placement and cholecystectomy) less than or equal to 2 weeks prior to the first NV1020 infusion and the patient must be clinically stable. Pump placement and cholecystectomy less than or equal to 1 week prior to the first NV1020 infusion
  8. Female who is pregnant or nursing
  9. Patients wishing to conceive within 2 months after the last infusion of NV1020
  10. Any investigational agent administered less than or equal to 4 weeks prior to NV1020 infusion
  11. Acute HSV infection requiring systemic antiviral therapy or history of serious HSV infection (e.g., ocular, encephalitic, etc.)
  12. Active viral hepatitis (evidence for infection with hepatitis A, B or C viruses)
  13. Known infection with HIV
  14. Known hypersensitivity to any component of the NV1020 formulation
  15. History of, or current, bleeding or coagulation disorder
  16. History of significant hepatic fibrosis, cirrhosis, or hemachromatosis
  17. History of malignancy other than colorectal cancer, within 5 years prior to start of study participation, with the exception of in situ cervical or skin carcinoma
  18. Active severe infection and any other concurrent disease or medical conditions that are likely to interfere with the study, as judged by the investigator
  19. Systemic corticosteroid administration < 4 weeks prior to starting NV1020 treatment
  20. Prior treatment with NV1020 or other putative oncolytic viruses
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00149396

Locations
United States, California
University of California, San Diego
San Diego, California, United States, 92093
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Pennsylvania
University of Pittsburgh Cancer Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
University of Vanderbilt
Nashville, Tennessee, United States, 37232
United States, Texas
Mary Crowley Medical Research Center
Dallas, Texas, United States, 75201
Sponsors and Collaborators
MediGene
Investigators
Study Director: Hoda Tawfik, PhD MediGene
  More Information

No publications provided by MediGene

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alice Chen, MediGene
ClinicalTrials.gov Identifier: NCT00149396     History of Changes
Other Study ID Numbers: CT1030
Study First Received: September 6, 2005
Last Updated: December 12, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by MediGene:
Colorectal cancer metastases to liver
Colorectal Cancer
Colorectal Carcinoma
Colorectal Tumors
Colorectal Neoplasms
Rectum Cancer
Rectum tumors
Rectum carcinoma
Colon cancer
Colon tumors
Colon carcinoma
Rectum Neoplasms
Colon Neoplasms
Liver Neoplasms
Hepatic Neoplasms
Liver Tumors
Liver cancer
Hepatic Cancer
Hepatic tumors
metastatic to the liver

Additional relevant MeSH terms:
Neoplasms
Colorectal Neoplasms
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Liver Diseases

ClinicalTrials.gov processed this record on September 29, 2014