N2001-03: CEP-701 in Treating Young Patients With Recurrent or Refractory High-Risk Neuroblastoma

• Status: Completed
• Trial end date: 2011-02-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: CEP-701 may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase I trial is studying the side effects and best dose of CEP-701 in treating young patients with recurrent or refractory high-risk neuroblastoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: New Approaches to Neuroblastoma Therapy Consortium
• Collaborator: National Cancer Institute (NCI)

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of neuroblastoma confirmed by at least 1 of the following:

• Histology

• Demonstrates clumps of tumor cells in the bone marrow with elevated urinary catecholamine metabolites

• Recurrent or resistant/refractory disease

• Neuroblastoma metastatic to the bone marrow with granulocytopenia, anemia, and/or thrombocytopenia allowed

• High-risk disease

• Patients in first response after completion of a prior front-line myeloablative regimen OR who were medically ineligible to receive a front-line myeloablative regimen must meet at least 1 of the following criteria:

• Viable neuroblastoma determined by biopsy of a persistent lesion as seen on CT scan, MRI, or metaiodobenzylguanidine (MIBG) scan

• If lesion was irradiated, biopsy must be performed at least 4 weeks after completion of prior radiotherapy

• Morphologic evidence of tumor in bone marrow

• Second or greater response (without histologic confirmation) allowed

• Meets at least 1 of the following criteria:

• At least 1 unidimensionally measurable lesion on CT scan, MRI, or X-ray

• At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

• MIBG scan with positive uptake at a minimum of 1 site

• Bone marrow with tumor cells on routine morphology (not by NSE staining only) of bilateral aspirate and/or biopsy AND/OR at least 5 tumor cells/10^6 mononuclear cells in the bone marrow by immunocytologic analysis of 2 consecutive bone marrows performed at least 1 day but no more than 4 weeks apart

PATIENT CHARACTERISTICS:

Age

• 21 and under at diagnosis

Performance status

• Karnofsky 50-100% (for patients > 16 years of age)

• Lansky 50-100% (for patients ≤ 16 years of age)

Life expectancy

• More than 2 months

Hematopoietic

• See Disease Characteristics

• Absolute neutrophil count ≥ 1,000/mm^3

• Platelet count ≥ 50,000/mm^3 (transfusion independent)

• Hemoglobin ≥ 8.0 g/dL (red blood cell transfusions allowed)

Hepatic

• ALT and AST ≤ 3.0 times upper limit of normal (ULN)

• Total bilirubin ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times normal OR

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 60 mL/min

Cardiovascular

• Ejection fraction ≥ 50% by echocardiogram or MUGA OR

• Fractional shortening ≥ 28% or above lower limit of normal by echocardiogram

Pulmonary

• Lung function normal

• No dyspnea at rest

• No exercise intolerance

• No supplemental oxygen requirement

Other

• Not pregnant

• Negative pregnancy test

• Fertile patients must use effective contraception

• No uncontrolled infection

• No other concurrent illness that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Chemotherapy

• At least 2 weeks since prior biologic or non-myelosuppressive therapy and recovered

• More than 7 days since prior growth factors

• No prior allogeneic stem cell transplantation AND no extensive chronic graft-versus-host disease

• No concurrent growth factors except filgrastim (G-CSF) or sargramostim (GM-CSF) administered for neutropenia lasting for more than 7 days or for confirmed or clinical septicemia associated with neutropenia

Chemotherapy

• At least 3 months since prior myeloablative chemotherapy with stem cell transplantation

• At least 2 weeks since prior chemotherapy and recovered

Endocrine therapy

• No concurrent corticosteroid therapy except replacement therapy for adrenal insufficiency or treatment for increased intracranial pressure

Radiotherapy

• See Disease Characteristics

• Recovered from prior radiotherapy

• At least 6 weeks since prior therapeutic-dose MIBG

• At least 6 weeks since prior craniospinal or other radiotherapy involving significant bone marrow (i.e., total pelvis or total abdomen)

• At least 4 weeks since prior radiotherapy to any site biopsied

• At least 2 weeks since prior local palliative radiotherapy (small port)

Surgery

• Not specified

Other

• No prior CEP-701

• No concurrent administration of any of the following CYP3A4 inhibitors:

• Cyclosporine

• Clotrimazole

• Ketoconazole

• Erythromycin

• Clarithromycin

• Troleandomycin

• HIV protease inhibitors

• Nefazodone

• Itraconazole

• Voriconazole