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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

Phase 1
18 Years
Open (Enrolling)
Colorectal Carcinoma

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Trial Information

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

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.

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.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the maximally-tolerated dose

Outcome Time Frame:

18 months

Safety Issue:


Principal Investigator

Young suk park, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Samsung Medical Center


Korea: Food and Drug Administration

Study ID:

SMC IRB 2009-06-055



Start Date:

September 2010

Completion Date:

October 2013

Related Keywords:

  • Colorectal Carcinoma
  • advanced/metastatic colorectal carcinoma
  • Carcinoma
  • Colorectal Neoplasms