HSV1716 in Patients With Non-Central Nervous System (Non-CNS) Solid Tumors
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, an oncolytic virus, 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 10^5 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 10^6 pfu directly into brain tumours. 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 intra-tumoural 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 dose of virus . Participates who experience at least stable disease or relapse following a determination of stable disease, may qualify for subsequent doses in PART 2. PART 2 requires signing of a separate consent.
Funding Source - FDA OOPD
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose Escalation Study of Intratumoral or Intravenous Herpes Simplex Virus-1 Mutant HSV1716 in Patients With Refractory Non-Central Nervous System (Non-CNS) Solid Tumors|
- 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. ] [ Designated as safety issue: Yes ]
- 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. ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2010|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Experimental: HSV1716 - Intratumoral route
Research participants with localized disease receiving HSV1716 as an intratumoral injection
Experimental: HSV1716 - intravenous
Research participants with metastatic disease receiving HSV1716 intravenously
|Contact: Melinda Lynn, RNfirstname.lastname@example.org|
|Contact: Amy Yekisaemail@example.com|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center||Recruiting|
|Cincinnati, Ohio, United States, 45229|
|Contact: James Geller, M.D. 513-636-6312 firstname.lastname@example.org|
|Principal Investigator: James Geller, M.D.|
|Nationwide Children's Hospital||Recruiting|
|Columbus, Ohio, United States, 43205|
|Contact: Timothy Cripe, MD, PhD 614-722-3552|
|Principal Investigator: Timothy Cripe, MD, PhD|
|Study Director:||Timothy Cripe, M.D., PhD.||Nationwide Children's Hospital|