A Phase 2b Study of Modified Vaccinia Virus to Treat Patients Advanced Liver Cancer Who Failed Sorafenib (TRAVERSE)

• ClinicalTrials.gov Identifier: NCT01387555
• Recruitment Status: Completed
• First Posted: July 4, 2011
• Last Update Posted: March 11, 2015
• Sponsor: Jennerex Biotherapeutics
• Information provided by (Responsible Party): Jennerex Biotherapeutics

Tracking Information

• First Submitted Date: June 27, 2011
• First Posted Date: July 4, 2011
• Last Update Posted Date: March 11, 2015
• Study Start Date: December 2008
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 6, 2012)

Survival [ Time Frame: CT scan every six weeks until progression or death, assessed up to 21 months ]

Determine overall survival for patients receiving JX-594 plus best supportive care (Arm A) compared with those patients receiving best supportive care (Arm B) in patients with advanced hepatocellular carcinoma (HCC) who have failed sorafenib treatment.

Original Primary Outcome Measures (submitted: July 1, 2011)

Survival [ Time Frame: CT scan every six weeks until progression or death, assessed up to 21 months ]

Determine overall survival for patients receiving JX-594 plus best supportive care (Arm A) compared with those patients receiving placebo plus best supportive care (Arm B) in patients with advanced hepatocellular carcinoma (HCC) who have failed sorafenib treatment.

Current Secondary Outcome Measures (submitted: April 10, 2013)

• Time to Tumor Progression [ Time Frame: CT scan every six weeks until progression or death, assessed up to 21 months ]
  Determine time-to-tumor-progression (TTP) for Arm A compared with Arm B based on mRECIST for HCC.
• Quality of Life [ Time Frame: assessed up to 21 months (average) ]
  Determine the Quality of Life (QoL) of patients treated in Arm A compared with Arm B.
• Tumor Response [ Time Frame: CT scan every 6 weeks until progression or death, assessed up to 21 months (average) ]
  Determine tumor response based on mRECIST for HCC of Arm A versus Arm B
• Safety profile of JX594 [ Time Frame: assessed up to 21 months (average) ]
  Safety will be assessed by the number of adverse events (AEs) and serious adverse events (SAEs)
• Time-to-symptomatic-progression [ Time Frame: assessed up to 21 months (average) ]
  Determine time to progression of Arm A compared to Arm B.

Original Secondary Outcome Measures (submitted: July 1, 2011)

• Time to Tumor Progression [ Time Frame: CT scan every six weeks until progression or death, assessed up to 21 months ]
  Determine time-to-tumor-progression (TTP) for Arm A compared with Arm B based on mRECIST for HCC.
• Quality of Life [ Time Frame: assessed up to 21 months (average) ]
  Determine the Quality of Life (QoL) of patients treated in Arm A compared with Arm B.
• Tumor Response [ Time Frame: CT scan every 6 weeks until progression or death, assessed up to 21 months (average) ]
  Determine tumor response based on mRECIST for HCC of Arm A verus Arm B
• Safety profile of JX594 [ Time Frame: assessed up to 21 months (average) ]
  Safety will be assessed by the number of adverse events (AEs) and serious adverse events (SAEs)
• Time-to-symptomatic-progression [ Time Frame: assessed up to 21 months (average) ]
  Determine time to progression of Arm A compared to Arm B.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 2b Study of Modified Vaccinia Virus to Treat Patients Advanced Liver Cancer Who Failed Sorafenib
• Official Title: A Phase 2b Randomized Trial of JX-594 (Vaccinia GM-CSF / TK-deactivated Virus) Plus Best Supportive Care Versus Best Supportive Care in Patients With Advanced Hepatocellular Carcinoma Who Have Failed Sorafenib Treatment
• Brief Summary: This study is to determine whether JX-594 (Pexa-Vec) plus best supportive care is more effective in improving survival than best supportive care in patients with advanced Hepatocellular Carcinoma (HCC) who have failed sorafenib.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Hepatocellular Carcinoma
• Liver Cancer
• HCC

Intervention

• Biological: JX-594 recombinant vaccina GM-CSF
  Patients will be randomised 2:1 to Arm A or Arm B and will receive 6 treatments on days 1, 8, 22, week 6, week 12, and week 18 plus best supportive care as needed.
• Other: Best Supportive Care
  Patients will be randomised 2:1 to Arm A or Arm B and will receive best supportive care as needed.

Study Arms

• Experimental: Arm A
  Patients on Arm A will receive 1 e9 pfu (plaque forming units) total dose of JX-594 (Vaccinia GM-CSF / TK-deactivated Virus) on each of six (6) treatments over 18 weeks.
  Intervention: Biological: JX-594 recombinant vaccina GM-CSF
• Arm B
  Patients on the control arm (Arm B) will have best supportive care over 18 weeks.
  Intervention: Other: Best Supportive Care

• Publications *: Moehler M, Heo J, Lee HC, Tak WY, Chao Y, Paik SW, Yim HJ, Byun KS, Baron A, Ungerechts G, Jonker D, Ruo L, Cho M, Kaubisch A, Wege H, Merle P, Ebert O, Habersetzer F, Blanc JF, Rosmorduc O, Lencioni R, Patt R, Leen AM, Foerster F, Homerin M, Stojkowitz N, Lusky M, Limacher JM, Hennequi M, Gaspar N, McFadden B, De Silva N, Shen D, Pelusio A, Kirn DH, Breitbach CJ, Burke JM. Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE). Oncoimmunology. 2019 Jun 3;8(8):1615817. doi: 10.1080/2162402X.2019.1615817. eCollection 2019.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 4, 2013): 129
• Original Estimated Enrollment (submitted: July 1, 2011): 120
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

KEY Inclusion Criteria:

• Diagnosis of primary HCC by tissue biopsy (histological/cytological diagnosis), or clinical diagnosis
• Previously treated with sorafenib for ≥ 14 days and has discontinued sorafenib treatment at least 14 days prior to randomization due to either intolerance or radiographic progression NOTE: Sorafenib is NOT required to be the most recent treatment received for HCC
• ECOG performance status 0, 1 or 2
• Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites
• Hematocrit ≥30% or Hemoglobin ≥10 g/dL
• Tumor status: Measurable viable tumor in the liver and injectable under imaging-guidance; At least one tumor in the liver that has not received prior local-regional treatment OR that has exhibited >25% growth in viable tumor size since prior local-regional treatment.

KEY Exclusion Criteria:

• Received sorafenib within 14 days prior to randomization
• Received systemic anti-cancer therapy other than sorafenib within 28 days of randomization
• Prior treatment with JX-594
• Platelet count < 50,000 PLT/ mm3
• Total white blood cell count < 2,000 cells/mm3
• Prior or planned organ transplant
• Known significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication
• Severe or unstable cardiac disease
• Viable CNS malignancy associated with clinical symptoms
• Pregnant or nursing an infant
• History of inflammatory skin condition (e.g., eczema requiring previous treatment, atopic dermatitis)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, France, Germany, Hong Kong, Korea, Republic of, Taiwan, United States
• Removed Location Countries: Italy, Spain

Administrative Information

• NCT Number: NCT01387555
• Other Study ID Numbers: JX594-HEP018
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jennerex Biotherapeutics
• Original Responsible Party: Theresa Hickman Clinical Project Manager, Jennerex, Inc.
• Current Study Sponsor: Jennerex Biotherapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: James Burke, MD; Jennerex Biotherapeutics

• PRS Account: Jennerex Biotherapeutics
• Verification Date: March 2015