NCT00931931: A Phase I Dose Escalation Study of Intratumoral Herpes Simplex Virus-1 Mutant HSV1716 In Patients with Refractory Non-Central Nervous System (Non-CNS) Solid Tumors Physician Friendly Version

What is the purpose of this study?

Primary
To determine whether intratumoral injection of HSV1716, at dose levels shown to be safe for adult tumors, is safe in adolescents and young adults with non-CNS solid tumors.

Time Frame: Dose limiting toxicities will be assessed at 28 days after injection of HSV1716.

Secondary
To measure antiviral immune response in patients with refractory cancer treated with HSV1716.

Time Frame: Antiviral immune response will be assessed 28 days after injection. Beginning at 1.5 years post injection, assessments will occur every 6 months. Beginning 5 years after the injection, assessments will occur annually until 15 years post injection.  

Who can participate?

Age: Subjects must be ≥13 years and ≤30 years of age at the time of signing consent (study entry).

  • Histologic Diagnosis: Subjects must have had histologic verification of a Non-CNS solid tumor at original diagnosis. The tumor must be amenable to HSV1716 administration without undue risk. Disease must be considered refractory to conventional therapy or for which no conventional therapy exists. There must be no available therapy with demonstrated clinical benefit for the subject as deemed by the subjects primary oncologist.
  • Metastatic Disease: Subjects who have metastasis to the brain are eligible for this study; however, no metastatic sites within the brain will be considered for injection.
  • Performance Level: Karnofsky ≥50. Subjects who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.
  • Life Expectancy: Anticipated to be ≥8 weeks from time of study entry.

Ages

  • From 13 To 30  years old

Conditions

  • Adult Studies
  • Cancer - Leukemia and Lymphoma
  • Vaccines

What is involved?

This is a single-site study.

Patients with relapsed solid tumors such as sarcomas and neuroblastoma have a poor survival, generally < 20%. There is an urgent need for new treatments that are safe and effective.

HSV1716 is a mutant herpes simplex virus (HSV) type I, deleted in the RL1 gene which encodes the protein ICP34.5, a specific determinant of virulence. Mutants lacking the RL1 gene are capable of replication in actively dividing cells but not in terminally differentiated cells - a phenotype exploited to selectively kill tumor cells. In previous clinical studies, HSV1716 has been shown to be safe when injected at doses up to 105 plaque forming units (pfu) directly into human high-grade glioma and into normal brain adjacent to tumour, following excision of high-grade glioma. In an extension study, HSV1716 has been shown to be safe when injected at a dose of up to 106 pfu directly into brain tumors. Replication of HSV1716 in human glioblastoma in situ has been demonstrated. Following a single administration of HSV1716 by direct injection into active recurrent tumor or brain adjacent to tumor, some patients have lived longer than might have been expected. This study seeks to evaluate the safety of a single injection of HSV1716 in the treatment of extracranial solid tumors in adolescents and young adults.

HSV1716 has also proved safe when given by direct intratumoral injection in patients with squamous carcinoma of the head and neck, and in patients with malignant melanoma.

Replication of HSV mutants in human sarcomas and neuroblastoma in cultured cells and human xenograft models has been demonstrated.

This study is designed in two parts. PART 1 of the study specifies a single virus injection. Participates who experience a partial response, or relapse following a complete response, may qualify for subsequent injections in PART 2, described in Section 16. PART 2 requires signing of a separate consent.

Who should I contact for more information?

Laura Mayer, MS CCRP 
Cincinnati Children’s Hospital Medical Center
Clinical Research Manager Division of Hematology/Oncology
Laura.Mayer@cchmc.org
513-636-9419

Where can I find additional information?

Principal Investigator

Timothy P. Cripe, MD, PhD Professor of Pediatrics
Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
timothy.cripe@cchm
513-636-4171