Safety Study of Recombinant Vaccinia Virus to Treat Refractory Solid Tumors in Pediatric Patients
Primary Purpose
Neuroblastoma, Rhabdomyosarcoma, Lymphoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)
Sponsored by
About this trial
This is an interventional treatment trial for Neuroblastoma focused on measuring 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
Eligibility Criteria
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 ultrasound)
- 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 eligible.
- 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)
Sites / Locations
- Cincinnati Children's Hospital Medical Center
- Texas Children's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single Arm - JX-594
Arm Description
Intratumoral injection of JX-594
Outcomes
Primary Outcome Measures
Determine the maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594
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
Determine the safety/toxicity of JX-594 administered by IT injection in this patient population
Secondary Outcome Measures
Determine the JX-594 pharmacokinetics and pharmacodynamics over time following IT injection in this patient population
Determine the immune response to JX-594 following IT injection in this patient population
Full Information
NCT ID
NCT01169584
First Posted
July 22, 2010
Last Updated
January 19, 2016
Sponsor
Jennerex Biotherapeutics
Collaborators
Solving Kids' Cancer
1. Study Identification
Unique Protocol Identification Number
NCT01169584
Brief Title
Safety Study of Recombinant Vaccinia Virus to Treat Refractory Solid Tumors in Pediatric Patients
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
November 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jennerex Biotherapeutics
Collaborators
Solving Kids' Cancer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase I, open-label, dose-escalation trial of JX-594 (Pexa-Vec) in pediatric patients with advanced/metastatic, unresectable solid tumors refractory to standard therapy and/or the patient does not tolerate standard therapies. Tumors are likely to include neuroblastoma, lymphoma, Wilms' tumor, rhabdomyosarcoma, Ewing's sarcoma, osteosarcoma, non-rhabdomyosarcoma soft tissue sarcomas, and malignant peripheral nerve sheath tumors. Benign tumors are excluded. These tumor types were selected because evidence of biological activity was observed in cancer cells lines and ex vivo infected primary human tissue samples, specifically pediatric cancer types such as sarcomas and neuroblastomas.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma, Rhabdomyosarcoma, Lymphoma, Wilm's Tumor, Ewing's Sarcoma
Keywords
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Arm - JX-594
Arm Type
Experimental
Arm Description
Intratumoral injection of JX-594
Intervention Type
Drug
Intervention Name(s)
Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)
Other Intervention Name(s)
Pexa-Vec
Intervention Description
Intratumoral Injection Dosage from 1 x 10^6 pfu/kg to 3 x 10^7 pfu/kg is administered once to 1-3 injectable tumors in pediatric patients.
Primary Outcome Measure Information:
Title
Determine the maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594
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
Time Frame
3 weeks
Title
Determine the safety/toxicity of JX-594 administered by IT injection in this patient population
Time Frame
3 weeks
Secondary Outcome Measure Information:
Title
Determine the JX-594 pharmacokinetics and pharmacodynamics over time following IT injection in this patient population
Time Frame
3 weeks
Title
Determine the immune response to JX-594 following IT injection in this patient population
Time Frame
3 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 ultrasound)
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 eligible.
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy Cripe, MD, PhD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-2399
Country
United States
12. IPD Sharing Statement
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Safety Study of Recombinant Vaccinia Virus to Treat Refractory Solid Tumors in Pediatric Patients
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