ADVL1322 (VEG116731) - A Phase II Study of Pazopanib (GW786034, NSC# 737754 in Children, Adolescents and Young Adults with Refractory Solid Tumors
Clinical Trial Information
Trial Contact: El-Shami, Jessica; Leffin, Melissa; Francois, Laetitia Claire; Spinelli, Jennifer
IRB No: 16.062.05
Protocol Abbrev: ADVL1322 (VEG116731)
Principal Investigator: Vincent F. Giusti, MD
Sub Investigators: Eslin, Don MD; Sutphin, Robert MD; Smith, Amy MD; Levy, Alejandro MD; Pope, Michele ARNP; Story, Allison ARNP; Wieber, Laura ARNP; Martin, Rebecca, ARNP; Sullivan, Kelly ARNP
Phase: Drug: Phase II
Age Group: Pediatric
Secondary Protocol No: ADVL1322 (VEG116731)
Applicable Disease Sites: Refractory Solid Tumors
Therapies Involved: Pazopanib
ClinicalTrials.gov ID: NCT01956669
The purpose of this study is to test the safety of pazopanib in children, adolescents and young adults. We want to find out what effects; good or bad, pazopanib has on patients aged from 12 months to 18 years of age, including how much of the drug gets into the blood stream and the lowest amount of drug that remains in your blood stream between doses. We will also look at whether your disease is stable or you have progression of your disease after you stop taking pazopanib.
Ages Eligible for Study: 1 Year to 18 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
• Subjects must be at least 1 and less than or equal to 18 years of age at the time of study entry.
• Subjects must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse - a) Rhabdomyosarcoma, b) Non-rhabdomyosarcomatous Soft Tissue Sarcoma (including desmoplastic small round cell tumor), c) Ewing Sarcoma / Peripheral Primitive Neuroectodermal Tumor (PNET), d) Osteosarcoma, e) Neuroblastoma (Measurable), f) Neuroblastoma (Evaluable), g) Hepatoblastoma. Note: Investigators are encouraged to enroll hepatoblastoma subjects on the appropriate COG biology study (eg: ABTR01B1) if they haven't already been enrolled and send available relapse tumor and/or blood samples in order to allow for future correlative biology studies in these subjects.
• Subjects who will be receiving the tablet formulation must have a body surface area (BSA) >= 0.84 m^2 (square meter) at the time of study enrollment.
• Subjects must have radiographically measurable disease (with the exception of neuroblastoma), Measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm).
• Subjects with neuroblastoma who do not have measurable disease but have iodine-131 - meta-iodobenzylguanidine positive (MIBG+) evaluable disease are eligible.
• Subjects must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2. Use Karnofsky for subjects >= 16 years of age and Lansky for subjects <= 16 years of age.
• Subjects must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• Subjects must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
• At least 7 days must have elapsed since the completion of therapy with a growth factor that supports platelet or white cell number or function. At least 14 days must have elapsed after receiving peg-filgrastim.
• At least 7 days must have elapsed since the completion of therapy with a biologic agent. For biologic agents that have known adverse events occurring beyond 7 days after administration, the period prior to enrollment must be extended beyond the time during which adverse events are known to occur.
• Subjects may have received bevacizumab, VEGF-Trap, or other VEGF blocking tyrosine kinase inhibitors, provided that they did not progress while receiving one of these agents. Subjects may not have previously received pazopanib.
• At least 21 days must have elapsed since the completion of the last dose of VEGF-Trap, and at least 7 days since a VEGF blocking tyrosine kinase inhibitor. Subjects must have recovered from any VEGF blocking drug-related toxicity (e.g., proteinuria).
• At least 3 half-lives of the antibody must have elapsed since prior therapy that included a monoclonal antibody.
• Radiotherapy: >=2 weeks must have elapsed since local palliative radiotherapy (XRT) (small port); >=3 months must have elapsed if prior Traumatic Brain Injury (TBI), craniospinal XRT or if >=50% radiation of pelvis; >=6 weeks must have elapsed if other substantial bone marrow irradiation was given.
• No evidence of active graft versus host disease and >=2 months must have elapsed since transplant or rescue
• Adequate Bone Marrow Function defined as peripheral absolute neutrophil count (ANC) >=1000/ microlitre (µL), platelet count >= 75,000/µL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment); and hemoglobin >= 8.0 grams (g)/decilitre (dL), may receive red blood cell (RBC) transfusions. Subjects with bone marrow involvement will be eligible for study (provided they meet the criteria) but will not be evaluable for hematologic toxicity.
• Adequate Renal and Metabolic Function defined as creatinine clearance or radioisotope Glomerular filtration rate (GFR) >= 70 millilitre (mL)/ (min)/1.73 meter (m)^2 or A serum creatinine based on age/gender as follows, age 1 to < 2 years (male-0.6 milligrams (mg)/dL, female-0.6 mg/dL), age 2 to < 6 years (male-0.8 mg/dL, female-0.8 mg/dL), age 6 to < 10 years (male-1 mg/dL, female-1 mg/dL), age 10 to < 13 years (male-1.2 mg/dL, female-1.2 mg/dL), age 13 to < 16 years (male-1.5 mg/dL, female-1.4 mg/dL), age >= 16 years (male-1.7 mg/dL, female-1.4 mg/dL), urine creatinine ratio of <1 or a urinalysis that is negative for protein; or, 24-hour urine protein level < 1000 mg/dL, no more than Grade 1 abnormalities of potassium, calcium (confirmed by ionized calcium), magnesium and phosphorous.
• Adequate Liver Function defined as total bilirubin <=1.5 x upper limit of normal (ULN) for age, serum glutamic-pyruvic transaminase (SGPT) Alanine transaminase (ALT) <=2.5 x ULN (for the purpose of this study, the ULN for SGPT is 45 U/L), Serum albumin >=2 g/dL. Must not have active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment). NOTE: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis. No known positivity of hepatitis B surface antigen (HBsAg), or of positive hepatitis C antibody.
• Adequate Cardiac Function defined as shortening fraction of >=27% by echocardiogram (while not receiving medications for cardiac function), or ejection fraction of >= 50% by gated radionuclide study (while not receiving medications for cardiac function), the corrected QTc interval by Bazett's formula (QTcB) <450 milliseconds (msec), and must not have a history of myocardial infarction, severe or unstable angina, peripheral vascular disease or familial QTc prolongation.
• Adequate Blood Pressure Control defined as a blood pressure (BP) <= the 95th percentile for age, height, and gender measured, subjects on stable doses of no more than one anti-hypertensive medication, with a baseline BP <= 95th percentile for age, height and gender, will be eligible.
• Central Nervous System (CNS) Function defined as subjects with a known history of seizures must have well-controlled seizures and may not be receiving enzyme-inducing anti-convulsants, CNS toxicity <= Grade 2.
• Adequate Coagulation defined as prothrombin time (PT) and partial thromboplastin time (PTT) <= 1.2 x upper limit of normal and an international normalized ratio (INR) <= 1.2.