Oncolytic HSV1716 in Treating Patients with Refractory Non-Central Nervous System Solid Tumors

Inclusion Criteria

• INCLUSION FOR INTRAMURAL INJECTION: * Subject must have lesion(s) amenable to HSV1716 administration by needle if superficial; by needle and/or catheter if deep or pulmonary, via interventional radiology without undue risk * Lesion(s) must meet size criteria * In the first two dose levels, subjects must have localized disease that meets size criteria; localized is defined as a single lesion; however, more than one lesion may be acceptable if they are contiguous * In the third dose level, subjects must have one to three lesions meeting size criteria * The arm (route of administration) will be chosen by the investigator and patient/parent based on multiple considerations and subject to approval by the principal investigator
• Subjects must have had histologic verification by a pathologist of cancer at original diagnosis; the tumor must be a non-CNS solid tumor; for subjects to be enrolled on the intratumoral arm, at least one lesion must be amenable to HSV1716 injection without undue risk, as determined by the interventional radiologist; disease must be considered refractory to conventional therapy or for which no conventional therapy exists
• Subjects who have metastasis to the brain are eligible for IV administration; however, any CNS lesion must be inactive; prior metastasis that has been treated and is no longer present is acceptable; no metastases to the CNS (brain or spine) of non-CNS solid tumors may be injected due to the potential for swelling at the injection site
• Lansky/Karnofsky >= 50 (Lansky for subjects 7 - 15 years; Karnofsky for subjects 16 - 30 years); 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
• Subjects must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: must not have received within 28 days of entry onto this study (42 days if prior nitrosourea drug) accompanied by hematopoietic recovery or 14 days of stopping non-myelosuppressive therapy as long as hematopoietic requirements are met
• Biologic (anti-neoplastic agent): must not have received within 7 days of entry onto this study (21 days if prior vascular endothelial growth factor (VEGF)-trap and at least 3 half-lives after last dose of a monoclonal antibody); for biologic agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
• No radiation therapy >= 14 days for local palliative radiation therapy (XRT) (small port): >= 6 months must have elapsed if prior craniospinal XRT or if >= 50% radiation of pelvis; >= 42 days must have elapsed if other substantial bone marrow radiation
• Immunoablative or myeloablative stem cell transplant (SCT): >= 6 months must have elapsed from prior autologous transplant; subjects must not have graft versus host disease post autologous transplant
• Investigational agent: >= 28 days must have elapsed from treatment with a different investigational agent
• Subjects with seizure disorder may be enrolled if on anticonvulsants and well controlled
• At the time of enrollment, specified baseline CNS conditions must be =< grade II toxicity per Common Terminology Criteria for Adverse Events (CTCAE) 3.0 criteria; this includes the following conditions: arachnoiditis/meningismus/radiculitis, ataxia, CNS cerebrovascular ischemia, CNS necrosis/cystid progression, cognitive disturbance, confusion, dizziness, encephalopathy, hydrocephalus, leak - cerebrospinal fluid, leukoencephalopathy (radiologic findings), mental status, psychosis, seizure, somnolence/depressed level of consciousness
• Peripheral absolute neutrophil count (ANC) >= 750/uL in absence of granulocyte colony stimulating factor (GCSF) for 72 hours (hrs) or pegylated (peg)-GCSF for 14 days
• Platelet count >= 100,000/uL (may be a post transfusion value)
• Hemoglobin >= 9.0 gm/dL (may be a post transfusion value)
• Serum creatinine =< 1.5 x upper limit of normal (ULN) for age or creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2
• Total bilirubin =< 2.0 x ULN for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x ULN for age
• Albumin >= 2g/dL
• Shortening fraction > 25% by echocardiogram or ejection fraction above the institutional lower limit of normal by multi gated acquisition scan (MUGA)
• No focal wall motion abnormalities as determined by either of the above studies
• Electrocardiography (EKG) without evidence of ischemia or significant arrhythmia
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.5 x ULN for age
• Documented evidence of negative tests for the presence of hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV)1 and HIV2 antibodies within the three months preceding study entry; subjects who do not have such evidence must undergo appropriate testing prior to virus administration
• The tumor volume must be a minimum of three times the injection volume; in the first and second dose levels, the lesion to be injected must be at least 18 mm in each of 3 dimensions as determined by computed tomography (CT) or magnetic resonance imaging (MRI) scans; lesions not meeting this requirement may be used if volumetric measurements show it to be >= 3 mL; in the third dose level, the lesion(s) to be injected must meet minimal tumor measurements and volume for each 1 mL fractionation of the injection volume (5mL); a single lesion meeting this requirement may be injected or the total volume may be distributed in up to 3 lesions meeting measurement and volume requirements as follows: * 5 mL of HSV1716; 30 mm minimum tumor length in each dimension; 15 mL minimum tumor volume * 4 mL of HSV1716; 28 mm minimum tumor length in each dimension; 12 mL minimum tumor volume * 3 mL of HSV1716; 26 mm minimum tumor length in each dimension; 9 mL minimum tumor volume * 2 mL of HSV1716; 23 mm minimum tumor length in each dimension; 6 mL minimum tumor volume * 1 mL of HSV1716; 18 mm minimum tumor length in each dimension; 3 mL minimum tumor volume ** Thus, the full 5 mL may be injected into a >= 15 mL tumor; 2 mL each may be injected into two >= 6 mL tumors plus 1 mL into a >= 3 mL, tumor, etc.; if a patient has multiple lesions but these criteria for injection cannot be met, they may be considered for the intravenous arm
• PART II; Subjects must have been enrolled in Part 1 of this study and have received 1 dose of HSV1716 and have completed at a minimum the day 28 follow-up; subjects must have been categorized at a minimum as having stable disease thought to be attributable to the virus; subjects who were minimally characterized as having stable disease are also eligible if their lesion re-occurs or re-grows; the same criteria will be applied to determine eligibility for a third dose, and again for a fourth dose
• PART II: The Part 2 consent must be signed

Exclusion Criteria

• No subjects who have received an allogeneic hematopoietic stem cell transplant are eligible
• Pregnant women are excluded and pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method from the time of study entry to a period of no less than four months post the final HSV1716 dose; for the same period of time, women who participate in this study must agree not to breast feed
• Unable or unwilling to give voluntary informed consent/assent
• Subjects with leukemia are not eligible for study participation
• Infection or any other severe systemic disease or medical or surgical condition deemed significant by the principal investigator
• Administration of any unlicensed or investigational agent within 4 weeks of entry to the study
• No PEGylated granulocyte colony stimulating factor (PEG-GCSF) within 14 days of virus administration (day 0)
• Subjects whose physicians determine that anti-HSV antiviral therapy (such as acyclovir, ganciclovir, foscarnet, etc.) cannot be safely discontinued from 2 days prior to being administered HSV1716 to 28 days following administration should not be in the study
• Subjects who have other conditions which in the opinion of the investigator contraindicate the receipt of HSV1716 or indicate subject’s inability to follow protocol requirements
• PART II: All eligibility requirements and exclusion criteria as described in PART 1 must be fulfilled within 14 days of receiving subsequent doses; testing completed from Part 1 may be accepted as long as completed within this time frame (+/- 1 day)