Safety Study of Recombinant Vaccinia Virus Administered Intravenously in Patients With Metastatic, Refractory Colorectal Carcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Samsung Medical Center
Information provided by (Responsible Party):
Jennerex Biotherapeutics
ClinicalTrials.gov Identifier:
NCT01380600
First received: June 22, 2011
Last updated: January 13, 2015
Last verified: March 2012
  Purpose

The purpose of this pilot safety study is to evaluate the safety and tolerability of JX-594 (Pexa-Vec) administered intravenously every 2 weeks in colorectal carcinoma patients who are refractory to or intolerant of oxaliplatin, irinotecan, and Erbitux treatments.


Condition Intervention Phase
Carcinoma, Colorectal
Drug: Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
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 Jennerex Biotherapeutics:

Primary Outcome Measures:
  • Determine the maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594 administered by biweekly intravenous (IV) infusion [ Time Frame: DLT evaluations through 14 days following last JX-594 treatment ] [ Designated as safety issue: Yes ]
    Any of the following treatment related adverse events: Grade 4 toxicity, Grade 3 hematologic toxicity for > 5 days, Grade 3 non-hematologic toxicities persisting for > 7 days except for flu-like symptoms that respond to standard therapies.

  • Determine the safety of JX-594 administered by biweekly IV infusion [ Time Frame: Safety evaluations through 28 days after last dose of JX-594 ] [ Designated as safety issue: Yes ]
    Adverse events will be collected and assessed to assess safety and tolerability through 28 days after last dose of JX-594 (or until all events considered probably or possibly related to JX-594 have resolved, stabilized, or returned to baseline status).


Secondary Outcome Measures:
  • Determine the pharmacokinetics, pharmacodynamics and immune response activity of JX-594 [ Time Frame: Blood samples collected at assigned time points from baseline through Week 8 ] [ Designated as safety issue: No ]
    Change over time in viral genomes, infectious units, GM-CSF concentration, peripheral white blood cell counts, plasma cytokine measurements, and neutralizing antibodies to JX-594 in blood and/or serum.

  • Determine the anti-tumoral response of JX-594 [ Time Frame: Disease control and response assessment at Week 8 ] [ Designated as safety issue: No ]
    Tumor response (Stable, partial, complete, progression) by standard RECIST on CT/MRI. Decrease in tumor blood marker.


Enrollment: 15
Study Start Date: July 2010
Estimated Study Completion Date: December 2015
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
single arm; Dose escalation
Dose escalation 1e6 pfu/kg bw, 1e7 pfu/kg bw, 3e7 pfu/kg bw of Recombinant Vaccinia GM-CSF JX-594
Drug: Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)
Intravenous Dose Range: 1x10^6 pfu/kg, 1x10^7 pfu/kg, 3x10^7 pfu/kg Up to 4 intravenous infusions administered over 60 minutes every 2 weeks.
Other Name: JX-594

  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 (if tumor advanced either immediately or within 3 months of the end of treatment)
  • Resistance to Erbitux: patients with Ras mutations, or for whom Erbitux has failed (if tumor advanced either immediately or within 3 months of the end of treatment, or there is no response to Erbitux therapy due to a lack of expression of EGFR (epidermal growth factor))
  • Karnofsky Performance Score (KPS) ≥ 70
  • Age ≥18 years
  • Laboratory Safety: 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 X ULN, INR ≤ 1.5, AST, ALT ≤ 2.5x ULN (in case of liver metastasis: AST,ALT ≤5.0 x ULN)
  • Serum chemistries within normal limits (WNL) or Grade 1 (excluding alkaline phosphatase) - If patients are diabetic, a fasting glucose must be done and patients must be > 160 mg/dL.
  • Patients who, if they are sexually active, are willing and able to refrain from sexual activity for 3 weeks following JX-594 administration. Patients who are willing and able to use a permitted contraceptive for 3 months after the final administration of JX-594.

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
  • Clinically uncontrolled and/or rapidly accumulating ascites, pericardial and/or pleural effusions
  • History of severe or unstable cardiac disease
  • Current, known CNS malignancy (history of completely resected or irradiated brain metastases by WBRT or stereotactic radiosurgery allowed)
  • Administered 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% Pulse oximetry O2 saturation <90% at rest
  • Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination
  • Pregnant or nursing
  • Household contact exclusions:
  • Women who are pregnant or nursing an infant
  • Children < 5 years 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)
  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: NCT01380600

Locations
Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Sponsors and Collaborators
Jennerex Biotherapeutics
Samsung Medical Center
  More Information

No publications provided

Responsible Party: Jennerex Biotherapeutics
ClinicalTrials.gov Identifier: NCT01380600     History of Changes
Other Study ID Numbers: JX594-IV-CRC014
Study First Received: June 22, 2011
Last Updated: January 13, 2015
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)
United States: Food and Drug Administration

Keywords provided by Jennerex Biotherapeutics:
Vaccinia
Vaccinia Virus
JX-594
Jennerex
Colorectal Carcinoma
Colorectal cancer
Colon Cancer
Rectal Cancer
Pexa-Vec

ClinicalTrials.gov processed this record on March 30, 2015