PATIENT CRITERIA:
Important Note: The eligibility criteria listed below are interpreted and cannot be waived (per COG policy posted 5/11/01). All clinical and laboratory data required for determining eligibility of a patient enrolled on this trial must be available in the patient's medical/research record which will serve as the source document for verification at the time of audit.
Age:
Patients must be less than 22 years of age at the time of enrollment.
Histologic Diagnosis:
Patients must have refractory (non-responsive) or relapsed neuroblastoma and have received all known curative treatment options and for which no additional therapy proven to prolong survival with an acceptable quality of life is available.
-Patients must have either a) histologic verification of neuroblastoma at initial diagnosis or relapse or b) demonstration of tumor cells in the bone marrow with increased urinary catecholamines at the time of initial diagnosis.
-Patients must have either a) evidence of disease progression (enlargement of existing measurable tumors or the appearance of new tumor) on the prior treatment regimen or b) if stable but non-responsive to the prior regimen, biopsy proven viable neuroblastoma at the time of enrollment.
-If a soft tissue or boney lesion was previously irradiated, either a) biopsy must be done at least 6 weeks after radiation and demonstrate viable neuroblastoma or b) growth in the lesion must be demonstrated by CT or MRI scan.
Patients must have disease per one of the following two strata criteria:
-Measurable Disease: Patients with radiographically measurable disease (by CT or MRI scan). Measurable tumor on MRI or CT or X-ray is defined as a minimum 20 mm in at least one dimension; for spiral CT, measurable disease is defined as minimum of 10 mm in at least one dimension, patients in this stratum may have additional disease evaluable by (123) I-MIGB scintigraphy, or
-Evaluable disease by (123) I-MIBG scintigraphy: For evaluable tumor, (123) I-MIBG must be positive at a minimum of one site. If the lesion was previously radiated, a biopsy must be done at least 6 weeks after radiation is complete and demonstrate viable neuroblastoma. Patients enrolled on this stratum must not have measurable disease by CT/MRI scan.
Performance Level:
Patients must have a performance status of 50%. Use Karnofsky for patients greater than 16 years of age and Lansky for patients less than or equal to 16 years of age.
Life Expectancy:
Patients must have a life expectancy of greater than or equal to 8 weeks.
Prior Therapy:
Patients must have fully recovered to Grade less than or equal to 1 (exceptions described below) from the acute toxic effects (based on CTCAE v3) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
a.) Myelosuppressive chemotherapy: Patients must not have received within 2 weeks of entry onto this study.
b.) Biologic (anti-cancer agent, example retinoids): At least 7 days since the completion of therapy with a biologic agent.
c.) Radiation (XRT): greater than or equal to 4 wks since last local palliative XRT (small port) or therapeutic radiolabeled (123) MIBG; greater than or equal to 6 wks must have elapsed if other substantial radiation (greater than 50% pelvis, craniospinal, total body radiation) was administered.
d.) Stem Cell Transplant (SCT): No evidence of active graft vs. host disease. For allogeneic SCT, greater than or equal to 4 months must have elapsed, and for autologous SCT greater than or equal to 2 months must have elapsed since transplant. (Infusion of autologous peripheral blood mononuclear cells without high dose chemotherapy or preparative regimen is not considered a stem cell transplant).
e.) Study specific limitations on prior therapy:
-There are no limitations on the number of prior chemotherapy regimens the patient could have received.
-Less than or equal to 30 days have elapsed since last dose of investigational drug therapy.
-Less than or equal to 30 days since immunotherapy (monoclonal antibody or vaccine) was administered.
Concomitant Medications Restrictions:
a.) Growth factor(s): Must not have been received within 1 week prior to entry onto this study.
b.) Study Specific:
-Patients must not receive other anti-cancer agents (investigational or approved) while on study. This includes cytotoxic agents or biological agents (retinoids).
-Palliative radiation is not permitted during enrollment on this study.
-Patients must not be receiving medication for the treatment of graft versus host disease (GVHD).
Organ Function Requirements:
All patients must meet the following criteria:
Adequate bone marrow function defined as: Hemoglobin greater than or equal to 7.5 g/dL (transfusions permitted), ANC greater than 250/microliter, platelet count greater than 25,000/microliter (without platelet transfusion support for greater than or equal to 7 days).
Adequate Renal Function Defined As:
-Creatinine clearance or radioisotope GFR greater than or equal to 60 ml/min/1.73m(2) or
-A serum creatinine based on age/gender as follows:
1 month to less than 6 months with a maximum serum creatinine of 0.4 for male and 0.4 for female.
6 months to less than 1 year with a maximum serum creatinine of 0.5 for male and 0.5 for female.
1 to less than 2 years with a maximum serum creatinine of 0.6 for male and 0.6 for female.
2 years to less than 6 years with a maximum serum creatinine of 0.8 for male and 0.8 for female.
6 to less than 10 years with a maximum serum creatinine of 1 for male and 1 for female.
10 to less than 13 years with a maximum serum creatinine of 1.2 for male and 1.2 for female.
13 to less than 16 years with a maximum serum creatinine of 1.5 for male and 1.4 for female.
Less than 16 years with a maximum serum creatinine of 1.7 for male and 1.4 for female.
Adequate liver function defined as:
-Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN) for age, and SGPT (ALT) less than 5 x upper limit of normal (ULN) for age.
Adequate cardiac function defined as:
-Shortening fraction of greater than or equal to 27% by echocardiogram.
Adequate neurologic function defined as:
-Patients with seizure disorder may be enrolled if receiving anticonvulsants and are well controlled.
-Neurologic toxicity from prior therapy (surgery, chemotherapy, or radiation) or tumor involvement must be Grade less than or equal to 2.
EXCLUSION CRITERIA:
Patients who are pregnant or breastfeeding are excluded because of potential adverse effects of ABT-751 on fetus and nursing infant.
Patients with documented allergy to sulfa containing medications are excluded.
Patients who have previously received ABT-751 are excluded.
Patients previously known to be HIV infected because of the potential suppression of the immune system by ABT-751 or drug interactions are excluded.
Patients with clinically significant unrelated systemic illness, such as serious infections, which, in the judgment of the treating physician, would compromise the patient's ability to tolerate the investigational agent or are likely to interfere with the study procedures or endpoints, are excluded.
Patients with elevated urinary catecholamines and/or bone marrow evidence of tumor, without measurable or evaluable disease by imaging modalities (CT, MRI, MIBG) are excluded.
Regulatory:
All Patients and/or their parents or legal guardians must sign a written informed consent.
All institutional, FDA, Health Canada, ICH/GCP, COG and NCI requirements for human studies must be met.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 09/15/2008