A Trial of JX-594 in Refractory Colorectal Carcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Young Suk Park, Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT01469611
First received: November 7, 2011
Last updated: June 12, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to:

  • determine the maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594 administered by biweekly intravenous (IV) infusion.
  • determine the safety of JX-594(TK- GM-CSF+ Wyeth strain vaccinia) administered by biweekly IV infusion.

Condition Intervention Phase
Colorectal Carcinoma
Biological: JX-594
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Dose Escalation Study of JX-594 (Thymidine Kinase-Inactivated Vaccinia Virus Plus GM-CSF) Administered by Biweekly (Every Two Weeks) Intravenous Infusion in Patients With Metastatic, Refractory Colorectal Carcinoma

Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • Determine the maximally-tolerated dose [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Determine the maximum-feasible dose [ Time Frame: 18months ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: September 2010
Estimated Study Completion Date: October 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: JX-594
Infusion Procedure:JX-594 will be administered on the designated treatment days at a dose of either 1 x 106, 1 x 107 or 3 x 107 pfu per kg. Virus infusion should occur over 60 minutes (+/- 5 minutes). The final infusion volume of virus plus diluent will be approximately 250 mL.
Biological: JX-594
Infusion Procedure:JX-594 will be administered on the designated treatment days at a dose of either 1 x 106, 1 x 107 or 3 x 107 pfu per kg. Virus infusion should occur over 60 minutes (+/- 5 minutes). The final infusion volume of virus plus diluent will be approximately 250 mL.

Detailed Description:

This is a Phase 1b, open-label, dose-escalation trial in patients with advanced colorectal carcinoma (CRC) that have failed both oxaliplatin based and irinotecan based prior chemotherapy regimens for metastatic disease. Patients will receive treatment at one of three dose levels in a sequential dose-escalating design.

Three patients will be treated at each dose level unless a dose-limiting toxicity (DLT) is observed. Enrollment will proceed to the next dose level if 0 of 3 patients experiences a DLT; if one of the first 3 patients experiences a DLT, additional patients will be enrolled until a second patient experiences a DLT (which defines the toxic dose) or until six total patients have been treated at that dose level, whichever comes first. If a second DLT is not experienced within that cohort, dose escalation may continue.

Patients will be enrolled a minimum of 14 days after the first treatment of the immediately preceding patient for the first patient in any cohort or all remaining patients in a cohort with DLT.

If 2 DLTs are observed within a cohort, enrollment into the cohort will cease and the dose level immediately preceding that dose will be determined to be the MTD. Regulatory Authorities and the IRB will be notified as required if any patient dies within 28 days of product administration due to a serious and unexpected ADR that is determined by the Investigator to be possibly or probably related to JX-594.

Once the MTD and/or MFD is defined, an additional 3-6 patients may be enrolled at that dose level. Note: once the MTD and/or MFD is defined, treatment of additional patients at this dose level will no longer require inter-patient delays of 14 days.

  Eligibility

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

Inclusion Criteria:

  • Histologically-confirmed, advanced/metastatic colorectal carcinoma
  • Failed both oxaliplatin and irinotecan based regimens for advanced/metastatic disease (tumor progression on or within 3 months of treatment completion)
  • Erbitux therapy resistant: Ras mutant tumor status, and/or failed Erbitux therapy (tumor progression on or within 3 months of treatment completion or Erbitux treatment not indicated due to lack of epidermal growth factor (EGFR) expression)
  • At least one measurable tumor mass by PET-CT/CT/MRI (lesion that can accurately be measured in at least one dimension with longest diameter > 1 cm)
  • Expected survival for approximately 12 weeks or longer
  • Karnofsky Performance Score (KPS) ≥ 70
  • Age ≥18 years
  • WBC ≥ 3,500 cells/mm3 and ≤ 50,000 cells/mm3
  • ANC ≥ 1,500 cells/mm3
  • Hemoglobin ≥ 10 g/dL (transfusion allowed)
  • Platelet count ≥ 100,000 plts/mm3
  • Total bilirubin ≤ 1.5 ULN
  • AST, ALT ≤2.5 ULN (if liver metastases(+): AST,ALT ≤5.0 x ULN)
  • Serum chemistries within normal limits (WNL) or Grade 1 (excluding alkaline phosphatase) - 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.

Exclusion Criteria:

  • Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids)
  • Known myeloproliferative disorders requiring systemic therapy
  • History of exfoliative skin condition (e.g. eczema or ectopic dermatitis) requiring systemic therapy
  • History of acquiring opportunistic infections.
  • Tumor(s) invading a major vascular structure (e.g. carotid artery)
  • Tumor(s) in location that would potentially result in significant clinical adverse effects if post-treatment tumor swelling were to occur (e.g. tumors impinging on the upper airway or affecting biliary tract drainage, etc.)
  • Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or pleural effusions
  • Severe or unstable cardiac disease, including (for example) coronary artery disease requiring increased doses of anti-anginal mediation and/or coronary angioplasty (including stent placement) within the preceding 24 months
  • Current, known CNS malignancy (history of completely resected or irradiated brain metastases by WBRT or stereotactic radiosurgery allowed)
  • Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case of mitomycin C or nitrosoureas)
  • Use of anti-viral, anti-platelet, or anti-coagulation medication [Patients who discontinue such medications within 7 days prior to first treatment may be eligible for this study.] Low dose aspirin (approximately 81 mg) allowed.
  • Pulse oximetry O2 saturation <90% at rest
  • Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination

Household contact exclusions:

  • Women who are pregnant or nursing an infant
  • Children < 12 months old
  • People with skin disease (e.g. eczema, atopic dermatitis, and related diseases Immunocompromised hosts (severe deficiencies in cell-mediated immunity, including AIDS, organ transplant recipients, hematologic malignancies)Patients with household contacts meeting any of the above criteria will be excluded unless alternate living arrangements can be made during the patient's dosing period and for at least 7 days following the last dose of study medication.
  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: NCT01469611

Locations
Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Sponsors and Collaborators
Samsung Medical Center
Investigators
Principal Investigator: Young suk park, MD Samsung Medical Center
  More Information

No publications provided

Responsible Party: Young Suk Park, Professor of Medicine, Sungkyunkwan University School of Medicine, Department of Hematology and Oncology, Samsung Medical Center
ClinicalTrials.gov Identifier: NCT01469611     History of Changes
Other Study ID Numbers: SMC IRB 2009-06-055
Study First Received: November 7, 2011
Last Updated: June 12, 2013
Health Authority: Korea: Food and Drug Administration

Keywords provided by Samsung Medical Center:
advanced/metastatic colorectal carcinoma

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on August 28, 2014