Phase II Trial of Vandetanib in Children and Adults With Wild-Type Gastrointestinal Stromal Tumors

Inclusion Criteria

• •Age:
• •greater than or equal to 3 years of age and Body Surface Area (BSA) greater than or equal to 0.5 m(2)
• •Diagnosis
• •Histologically or cytologically confirmed Gastrointestinal Stromal Tumors (GIST) by the Laboratory of Pathology, National Cancer Institute (NCI).
• •Absence of Kit and platelet derived growth factor receptor alpha (PDGFRA) mutation confirmed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory.
• •Participants must have measurable disease as defined in Response Evaluation Criteria in Solid Tumors (RECIST (v1.1) as the presence of at least one lesion not previously irradiated, that can be accurately measured at baseline greater than or equal to 10mm in the longest diameter (except lymph nodes which must have short axis greater than or equal to 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
• •Prior therapy:
• •Participants must be at least 4 weeks from prior surgical procedures and surgical incisions must be healed.
• •Participants must have had their last fraction of external beam radiation therapy at least 4 weeks prior to enrollment.
• •Participants must have had their last dose of cytotoxic chemotherapy at least 28 days prior to enrollment, their last dose of biological therapy, such as biological response modifiers (e.g., cytokines), immunomodulatory agents, vaccines, differentiating agents, used to treat their cancer at least 7 days prior to enrollment, their last dose of a monoclonal antibody at least 30 days prior to enrollment, and their last dose of any investigational agent at least 30 days prior to enrollment.
• •Participants must have received their last dose of short acting colony stimulating factor, such as filgrastim or sargramostim at least 72 hours prior to enrollment and their last dose of long-acting colony stimulating factors, such as PEG-filgrastim at least 7 days prior to enrollment.
• •Participants must have recovered from the acute toxic effects of prior therapy to a grade 1 (Common Terminology Criteria in Adverse Events (CTCAE v.4.0)) level prior to enrollment (does not apply to alopecia).
• •Performance Status: Lansky (for participants 10 years of age or younger) or Karnofsky (for participants older than 10 years) performance score greater than 50
• •Patients must have normal organ and marrow function as defined below:
• •Hematological Function: The peripheral absolute neutrophil count must be at least 1,500/microL and the platelet count must be at least 100,000/microL within 72 hours prior to enrollment.
• •Coagulation: Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) must not be more than 1.5 x upper limit of normal (ULN) within 72 hours prior to enrollment. PT and PTT should drawn by venipuncture, rather than from a central venous catheter when feasible.
• •Hepatic Function: Bilirubin must not be more than 1.5 x ULN (does not apply to patients with Gilberts Disease) and the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must not be more than 2.5 x ULN within 72 hours prior to enrollment, or greater than 5.0 X ULN if in the Investigator s judgment it is related to liver metastases. AST and ALT may be up to 5 x ULN within 72 hours prior to enrollment in participants with hepatic metastases.
• •Renal Function: Participants must have an age-adjusted normal serum creatinine (see Table) or a creatinine clearance of at least 50 ml/min/1.73 m(2).
• •Age (years) Male Female
• •3 to 5 = .42
• •5 to \<10 = 1
• •10 to \<13 = 1.2
• •13 to \<16 = 1.5 male and 1.4 female
• •16 and older = 1.7 male and 1.4 female
• •Hypertension:
• •Participants should have normal blood pressure according to age. Participants 18 years of age and younger should have a blood pressure 95th percentile for age, height and gender, and should not be receiving medication for treatment of hypertension. Preexisting hypertension in adults should be controlled (either with pharmacological or non-pharmacological methods) at the time of enrollment.
• •Birth Control:
• •Participants of child-bearing or child-fathering potential must be willing to use a medically effective form of birth control, which includes abstinence, while taking vandetanib and for 4 months after the last dose. \[Female patients must be 1 year postmenopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign the informed consent form \[ICF\]) and for 3 months after the last dose of vandetanib to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.
• •Male patients must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign the ICF) and for 4 months after the last dose of vandetanib to prevent pregnancy in a partner.\]
• •Negative pregnancy test for women of childbearing potential.
• •Informed Consent:
• •Participants who are greater than or equal to 18 years of age or Legally Authorized Representative (LAR) of participants who are younger than 18 years must sign an informed consent for the Pediatric Oncology Branch (POB) Screening Protocol (01-C-0157: Eligibility Screening and Tissue Procurement for the National Cancer Institute (NCI), Pediatric Oncology Branch (POB) Clinical Research Protocols) prior to participating in studies required to determine eligibility for this trial. After confirmation of eligibility, participants who are greater than or equal to 18 years of age or LAR of minor participants must sign an informed consent document for this trial, indicating that they are aware of the investigational nature of the proposed treatment, the risks and benefits of participating and the alternatives to participating, prior to the conduct of any study procedures.