Safety Study of Recombinant Vaccinia Virus to Treat Refractory Solid Tumors in Pediatric Patients

NCT01169584 | Completed Phase 1 DMC

• 1 other identifier: JX594-IT-P009
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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

  3 weeks

• Determine the safety/toxicity of JX-594 administered by IT injection in this patient population

  3 weeks

Secondary Outcomes (2)

• Determine the JX-594 pharmacokinetics and pharmacodynamics over time following IT injection in this patient population

  3 weeks

• Determine the immune response to JX-594 following IT injection in this patient population

  3 weeks

Study Arms (1)

Single Arm - JX-594

EXPERIMENTAL

Intratumoral injection of JX-594

Drug: Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)

Interventions

Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594) DRUG

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.

Also known as: Pexa-Vec

Single Arm - JX-594

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Jennerex Biotherapeutics: lead
• Solving Kids' Cancer: collaborator

Study Sites (2)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Texas Children's Hospital

Houston, Texas, 77030-2399, United States

Location

MeSH Terms

Conditions

Neuroblastoma; Rhabdomyosarcoma; Lymphoma; Wilms Tumor; Sarcoma, Ewing; Vaccinia; Osteosarcoma; Neurofibrosarcoma

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neurofibroma; Nerve Sheath Neoplasms; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Study Officials

• Timothy Cripe, MD, PhD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2010
• First Posted: July 26, 2010
• Study Start: August 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: November 1, 2014
• Last Updated: January 21, 2016

Record last verified: 2016-01

Locations

US (2)