A Study of Recombinant Vaccinia Virus to Treat Unresectable Primary Hepatocellular Carcinoma

NCT00554372 | Completed Phase 2 Results DMC

• 1 other identifier: JX594-IT-HEP007
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 9

Brief Summary

The purpose of this research study is to determine whether JX-594 (Pexa-Vec) has significant anti-tumoral activity and tolerability in primary hepatocellular carcinoma and to determine the dose to be used in further testing.

Conditions

Carcinoma, Hepatocellular

Keywords

Jennerex; HCC; unresectable primary hepatocellular carcinoma; hepatocellular carcinoma; liver cancer; Phase 2; oncolytic virus; Pexa-Vec

Outcome Measures

Primary Outcomes (1)

• Proportion of Subjects Achieving Disease Control (Non-progressive Disease) at 8 Weeks After Initiation of Treatment

  Proportion of subjects achieving disease control at 8 weeks based on a modified Response Evaluation Criteria in Solid Tumors v1.0 (mRECIST). Per mRECIST for target lesions as assessed by dynamic contrast enhanced dynamic MRI: Complete Response (CR), Disappearance of all tumor(s); Partial Response (PR), \>=30% decrease in the sum of longest diameter (LD) of tumor(s) taking as reference the baseline sum; Stable Disease (SD), any cases that do not qualify for PR or progressive disease (PD); PD, any increase of \>= 20% in the sum of longest diameter (LD) of tumor(s) taking as reference the baseline sum. Disease Control (DC) = CR or PR or SD. For mRECIST criteria, new tumor(s) that developed within the liver were measured (a new tumor was defined as a malignant tumor not present at baseline, was ≥ 1 cm in LD had typical hypervascular features of HCC). Their maximum diameter(s) were included in the sum of the maximum diameter; new tumors were not considered evidence for progression.

  Initial progression status and response assessment at 8 weeks from first dose

Secondary Outcomes (3)

• Safety and Tolerability of JX-594 Administered at Two Dose Levels

  Safety and tolerability were evaluated throughout the 8 week period of study participation

• Number of Subjects Achieving Disease Control as Determined Using Intrahepatic Modified RECIST Criteria

  At week 8

• Median Overall Survival

  To 760 days post treatment

Study Arms (2)

Low Dose

EXPERIMENTAL

1e8 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart)

Genetic: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)

High Dose

EXPERIMENTAL

1e9 pfu (plaque-forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart)

Genetic: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)

Interventions

JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF) GENETIC

Patients will be randomized 1:1 to one of two total doses (1e8 or 1e9 pfu)and injected intratumorally in 1-5 intrahepatic tumors on Days 1, 15, and 29.

High Dose; Low Dose

Eligibility Criteria

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

You may qualify if:

• Histological confirmation or clinical/laboratory diagnosis of primary hepatocellular carcinoma (HCC)
• Cancer is not surgically resectable for cure
• Child Pugh A or B
• Tumor progression during or after at least one prior HCC treatment regimen (Note: If standard HCC therapies are either medically contraindicated or patient has refused those treatments, the patient may be eligible for this study)
• Performance Score: KPS score of ≥ 70
• Anticipated survival of at least 16 weeks
• Total bilirubin ≤ 2.5 x ULN
• AST, ALT \< 5.0 x ULN
• WBC \> 2,500 cells/mm3 and \< 50,000 cells/mm3 (GCSF treatment allowed)
• ANC \> 1,250 cells/mm3 (GCSF treatment allowed)
• Hemoglobin ≥ 9 g/dL (RBC transfusion allowed)
• Platelet count ≥ 50,000 plts/mm3
• Acceptable coagulation status: INR ≤ 1.5 x ULN
• Acceptable kidney function: Serum creatinine \< 2.0 mg/dL
• If patients are diabetic or have a screening random glucose \> 160 mg/dL, a fasting glucose must be done and patients must be WNL or Grade 1 in order to be eligible for the study

You may not qualify if:

• Current, known extra-hepatic tumors that, in the investigator's medical opinion, are likely to result in significant morbidity or mortality within the next 16 weeks.
• Pregnant or nursing an infant
• Known infection with HIV
• Clinically significant active infection or uncontrolled medical condition considered high risk for investigational new drug treatment
• Significant immunodeficiency due to underlying illness (e.g. hematological malignancies, congenital immunodeficiencies and/or HIV infection/AIDS) and/or medication (e.g. high-dose systemic corticosteroids)
• History of exfoliative skin condition (e.g. severe eczema, ectopic dermatitis, or similar skin disorder) that at some stage has required systemic therapy
• Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or pleural effusions
• Liver tumors in a location that would potentially result in significant clinical adverse effects if post-treatment tumor swelling were to occur (e.g. tumors impinging on the biliary tract that could affect drainage)
• Severe or unstable cardiac disease
• Current, known CNS malignancy
• Anti-cancer therapy (e.g. RFA, TACE, PEIT, radioembolization, chemotherapy, surgery, or an investigational drug, etc.) within 4 weeks prior to first treatment
• Absolute contraindication to undergoing MRI scanning
• Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination
• Use of anti-platelet or anti-coagulation medication
• Use of the following anti-viral agents: ribavirin, adefovir, cidofovir (within 7 days prior to the first treatment), and PEG-IFN (within 14 days prior to the first treatment).

Sponsors & Collaborators

• Jennerex Biotherapeutics: lead

Study Sites (9)

Moores UCSD Cancer Center

La Jolla, California, 92093, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Billings Clinic Cancer Center

Billings, Montana, 59101, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Medical Center - Liver Cancer Center

Pittsburgh, Pennsylvania, 15213, United States

Location

McMaster University Medical Centre

Hamilton, Ontario, L8N 1Y3, Canada

Location

Pusan National University Hospital

Busan, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Shin Chon Severance Hospital / Yonsei University Medical Center

Seoul, South Korea

Location

Related Publications (2)

• Heo J, Reid T, Ruo L, Breitbach CJ, Rose S, Bloomston M, Cho M, Lim HY, Chung HC, Kim CW, Burke J, Lencioni R, Hickman T, Moon A, Lee YS, Kim MK, Daneshmand M, Dubois K, Longpre L, Ngo M, Rooney C, Bell JC, Rhee BG, Patt R, Hwang TH, Kirn DH. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat Med. 2013 Mar;19(3):329-36. doi: 10.1038/nm.3089. Epub 2013 Feb 10.

  PMID: 23396206 RESULT

• Breitbach CJ, Arulanandam R, De Silva N, Thorne SH, Patt R, Daneshmand M, Moon A, Ilkow C, Burke J, Hwang TH, Heo J, Cho M, Chen H, Angarita FA, Addison C, McCart JA, Bell JC, Kirn DH. Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans. Cancer Res. 2013 Feb 15;73(4):1265-75. doi: 10.1158/0008-5472.CAN-12-2687. Epub 2013 Feb 7.

  PMID: 23393196 DERIVED

Related Links

• Sponsor company website
• Sponsor company was acquired by SillaJen Inc.

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Manager, IP, Contracts, Translational Research
• Organization: SillaJen Biotherapeutics, Inc.

tchiaverotti@sillajen.com

415 281 8886

Study Officials

• David Kirn, MD

  Jennerex Biotherapeutics

  STUDY DIRECTOR

• Tony Reid, Md, PhD

  University of California San Diego, Moores Cancer Center

  PRINCIPAL INVESTIGATOR

• Jeong Heo, MD, PhD

  Pusan National University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2007
• First Posted: November 6, 2007
• Study Start: August 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: February 1, 2013
• Last Updated: February 4, 2016
• Results First Posted: August 17, 2015

Record last verified: 2011-10

Locations

US (5); KR (3); CA (1)