Phase I Trial of CEDIRANIB (AZD2171), an Orally Bioavailable Antiangiogenic Agent, in Children and Adolescents With Refractory or Recurrent Solid Tumors
Phase I Trial of CEDIRANIB (AZD2171), an Orally Bioavailable Antiangiogenic Agent, in Children and Adolescents With Refractory or Recurrent Solid Tumors
Background:
Objectives:
Eligibility:
-Children and adolescents 2-18 years of age with treatment-resistant solid tumor cancers or acute myelogenous leukemia.
Design:
Background:
Objectives:
Eligibility:
-Children and adolescents (greater than 2 yrs and less than 19 years of age) with histologically confirmed relapsed or refractory extracranial solid tumors that are measurable or evaluable.
Design:
AGE: Patients must be greater than 2 years and less than 19 years of age.
DIAGNOSIS: Solid Tumors (dose escalation component of the trial): Histologically confirmed extracranial malignant solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, and germ cell tumors.
DISEASE STATUS: Patients with solid tumors must have measurable or evaluable disease.
- Patients must be able to swallow tablets intact.
PRIOR THERAPY: The patient's cancer must have relapsed after or failed to respond to frontline standard therapy and no other standard curative treatment options are available. Standard therapy may include surgery, radiation therapy, chemotherapy, or any combination of these modalities.
Patients must have had their last fraction of radiation therapy:
Patients must have had their last dose of:
Cytotoxic chemotherapy:
-Patients with solid tumors, the last dose of cytotoxic therapy must be at least 21 days prior to study entry.
Biological therapy that was administered for the treatment of cancer at least 7 days prior to study entry.
Immunotherapy (antibody) at least 30 days prior to study entry.
Any investigational cancer therapy at least 30 days prior to study entry.
Patients who have received an allogeneic BM or SC transplant must be at least 3 months post-transplant; and patients who have received an autologous BM or SC transplant must be at least 2-months post-transplant.
Patients must have recovered from the acute toxic effects of prior therapy before entry onto this trial.
Patients should be off colony stimulating factors such as filgrastim (G-CSF), sargramostim (GM-CSF), and IL-11 (with the exception of erythropoietin) for at least 72 hours prior to study entry. Patients receiving PEG-filgrastim (Neulasta ) must be at least 7 days from the last dose.
CONCOMITANT MEDICATIONS:
PERFORMANCE STATUS: Patients greater than 10 years old must have a Karnofsky performance level greater than 50, and children less than or equal to 10 years old must have a Lansky performance level greater than 50.
HEMATOLOGICAL FUNCTION:
-Patients with solid tumors must have adequate bone marrow function, defined as a peripheral absolute neutrophil count of greater than or equal to 1,500/microL, and a platelet count greater than or equal to 100,000/microL (transfusion independent).
Coagulation: Patients must have adequate hemostatic function defined as PT and PTT less than or equal to 1.5 x ULN. It is recommended that PT and PTT be drawn by peripheral venipuncture rather than from an indwelling central venous catheter.
CARDIAC: Patients must have:
HEPATIC FUNCTION: Patients must have adequate liver function, defined as bilirubin less than or equal to 1.5 x ULN, SGPT (ALT) less than or equal to 2.5 x ULN.
RENAL FUNCTION:
Proteinuria less than or equal to 1 + on dipstick when urine specific gravity is less than or equal to 1.015 or 24 hr urine total protein is less than or equal to 500 grams/24hr.
Patients must have an age-adjusted normal serum creatinine (See Table Below) OR a creatinine clearance is greater than or equal to 60 mL/min/1.73 m(2).
2 to less than 6 years of age equals a maximum serum creatinine of 0.8 mg/dl.
6 to less than 10 years of age equals a maximum serum creatinine of 1 mg/dl.
10 to less than 13 years of age equals a maximum serum creatinine of 1.2 mg/dl.
13 years to less than 16 years of age equals a maximum serum creatinine of 1.5 mg/dl (male) and 1.4 mg/dl (female).
Greater than or equal to 16 years of age equals a maximum serum creatine of 1.7 mg/dl (male) and 1.4 mg/dl (female).
INFORMED CONSENT: All patients or their legal guardians (if the patient is less than 18 years old) must sign a document of informed consent (Pediatric Oncology Branch, NCI screening protocol for NIH patients) prior to performing studies to determine patient eligibility. After confirmation of patient eligibility all patients or their legal guardians must voluntarily sign the IRB approved protocol specific informed consent to document their understanding of the investigational nature and the risks of this study before any protocol related studies are performed (other than the studies which were performed to determine patient eligibility).
DURABLE POWER OF ATTORNEY (DPA): Patients who are 18 years of age will be offered the opportunity to assign a DPA so that another person can make decisions about their medical care if they become incapacitated or cognitively impaired.
BIRTH CONTROL: Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are receiving protocol therapy and for 2 weeks after the last dose of Cediranib.
EXCLUSION CRITERIA:
Patients with primary brain tumors.
Patients with a history of congenitally prolonged QTc, or history of arrhythmia (multifocal premature ventricular contractions, bigeminy,trigeminy, ventricular tachycardia, uncontrolled atrial fibrillation, left bundle block) that is symptomatic or requires treatment (except for controlled atrial fibrillation).