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A Phase I, Open-Label, Dose Escalation Study of JX-594 (Vaccinia GM-CSF/Thymidine Kinase-Deactivated Virus) Administered by Intratumoral Injection in Pediatric Patients With Unresectable Refractory Solid Tumors.

Phase 1
2 Years
21 Years
Open (Enrolling)
Neuroblastoma, Rhabdomyosarcoma, Lymphoma, Wilm's Tumor, Ewing's Sarcoma

Thank you

Trial Information

A Phase I, Open-Label, Dose Escalation Study of JX-594 (Vaccinia GM-CSF/Thymidine Kinase-Deactivated Virus) Administered by Intratumoral Injection in Pediatric Patients With Unresectable Refractory Solid Tumors.

Inclusion Criteria:

- Age between 2 and 21 years

- Histologically-confirmed, advanced/metastatic non-CNS solid tumor that is relapsed
and/or refractory to standard therapy (progressive disease despite therapy) and/or
the patient does not tolerate standard therapy. Non-CNS solid tumors are eligible and
are likely to include such histologies as neuroblastoma, Wilms' tumor,
rhabdomyosarcoma, Ewing's sarcoma, osteosarcoma, non-rhabdomyosarcoma soft tissue
sarcomas, and malignant peripheral nerve sheath tumors.

- Cancer is not surgically resectable for cure

- At least one measurable tumor mass by CT/MRI (i.e. lesion that can accurately be
measured in at least one dimension with longest diameter ≥ 1 cm) and that can be
injected by direct visualization/palpitation or by imaging-guidance (CT or

- Expected survival for approximately 8 weeks or longer

- Lansky Score ≥ 50

- Total bilirubin ≤ 2.5 × ULN

- AST, ALT ≤ 2.5 × ULN (if liver tumor(s) present: AST/ALT ≤ 5 x ULN)

- Serum creatinine ≤ 1.8 x ULN

- INR ≤ 1.5 x ULN

- Hematologic parameters: Patients can be transfused to meet these entry criteria.

- Hemoglobin ≥ 9 g/dL

- For bone marrow negative patients: ANC ≥ 750 cells/ mm3 and platelet count ≥
75,000 plts/mm3

- For bone marrow positive patients: ANC ≥ 750 cells/ mm3. Platelet count recovery
is not a requirement, but platelets should be transfused to ≥ 75,000 plts/ mm3
prior to treatment.

- CD4 count ≥ 200/mm3. Patients who demonstrate intact delayed-type hypersensitivity
(DTH) via skin immune response to common antigens (e.g. candida, mumps) are also

- For patients who are sexually active, able and willing to abstain from sexual
activity for 3 weeks following treatment with JX-594. Thereafter, able and willing to
use accepted birth control methods through 3 months after last treatment with JX-594.
[Acceptable birth control methods include contraceptive pills, condom, IUD, diaphragm
or sponge + spermicide, or other methods with >97% effectiveness]

- Able and willing to sign an Institutional Review Board (IRB)/Research Ethics Board
(REB)-approved written consent form (patient and/ or parents/guardians).

- Able and willing to comply with study procedures and follow-up examinations,
including compliance with the "Infection Control Guidelines for Patients" contained
within the written consent form (patient and/ or parents/guardians).

Exclusion Criteria:

- Pregnant or nursing infant

- Injected tumor(s) in location that would potentially result in significant clinical
adverse effects if post-treatment tumor swelling were to occur or if deemed unsafe by
investigator (e.g. tumors impinging on the upper airway or affecting biliary tract
drainage, adherent to and/or invading a major vascular structure, CNS, etc.)

- Brain metastases, unless surgically resected and/or irradiated. (Brain metastases
cannot be considered as a site for injection).

- Patients with lymphomas

- Use of high dose systemic corticosteroids or other immune suppressive medication
within 3 weeks of first treatment (e.g. cortisone, dexamethasone, hydrocortisone,
prednisone, prednisolone, interferon, cisplatin, doxorubicin, fluorouracil, etc.). *
Note: patients taking low-dose corticosteroids for the treatment of nausea and/or
taking maintenance corticosteroids for adrenal insufficiency are permitted to enroll.

- Known infection with HIV or known underlying genetic immunodeficiency disease

- Treatment of the injected tumor(s) with radiotherapy, chemotherapy, surgery, or an
investigational drug within 3 weeks prior to first treatment

- Clinically significant active infection or uncontrolled medical condition considered
high risk for investigational new drug treatment (e.g. pulmonary, neurological,
cardiovascular, gastrointestinal, genitourinary)

- History of exfoliative skin condition (e.g. severe eczema, ectopic dermatitis, or
similar skin disorder) requiring systemic therapy

- Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or
pleural effusions (e.g. requiring drainage for symptom control)

- Severe or unstable cardiac disease which may include, but is not limited to, any of
the following within 6 months prior to screening: myocardial infarct, unstable
angina, congestive heart failure, myocarditis, arrhythmias diagnosed and requiring
medication, or any clinically-significant change in cardiac status

- Current, active, progressing CNS malignancy, including carcinomatosis meningitis
(definitively surgically resected or irradiated metastases allowed)

- Pulse oximetry O2 saturation <90% at rest

- Use of anti-viral, anti-platelet or anti-coagulation medication (for example,
heparin, warfarin, aspirin, ticlopidine, clopidogrel, dipyridamole) [Patients who
discontinue such medications within 7 days prior to first treatment may be eligible
for this study. Any required, chronic medications indicated for other medical issues
should not be discontinued in order to meet eligibility criteria for this trial
without consultation with both the patient and the treating physician.] Note: Low
Dose Heparin to maintain patency of venous catheters is permitted.

- Patients with benign tumors

- Inability or unwillingness to give informed consent (patient or parent/guardian) or
comply with the procedures required in this protocol

- Vaccination with a live virus (i.e. measles, mumps, rubella, etc) < 30 days prior to
first treatment

- Patients with household contacts who meet any of these criteria will be excluded
unless alternate living arrangements can be made during the patient's active dosing
period and for three weeks following the last dose of study medication:

- Women who are pregnant or nursing an infant

- Children < 1 years old

- People with skin disease (eczema, atopic dermatitis and related diseases)

- Immunocompromised hosts (severe deficiencies in cell-mediated immunity,
including AIDS, organ transplant recipients, hematologic malignancies)

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594

Outcome Description:

Determine the maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594 administered by intratumoral (IT) injection in pediatric patients with advanced/metastatic, unresectable refractory solid tumors

Outcome Time Frame:

3 weeks

Safety Issue:


Principal Investigator

Timothy Cripe, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Hospital Medical Center, Cincinnati


United States: Food and Drug Administration

Study ID:




Start Date:

August 2010

Completion Date:

September 2013

Related Keywords:

  • Neuroblastoma
  • Rhabdomyosarcoma
  • Lymphoma
  • Wilm's Tumor
  • Ewing's Sarcoma
  • Phase I
  • advanced metastatic pediatric solid tumors
  • pediatric
  • vaccinia virus
  • oncolytic virus
  • neuroblastoma
  • rhabdomyosarcoma
  • lymphoma
  • Wilm's tumor
  • Ewing's sarcoma
  • osteosarcoma
  • non-rhabdomyosarcoma soft tissue sarcomas
  • malignant peripheral nerve sheath tumors
  • Pexa-Vec
  • Lymphoma
  • Wilms Tumor
  • Neuroblastoma
  • Rhabdomyosarcoma
  • Vaccinia
  • Sarcoma, Ewing's
  • Neuroectodermal Tumors, Primitive, Peripheral
  • Sarcoma



Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Texas Children's Hospital Houston, Texas