Expired Study
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Palo Alto, California 94305


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.

Study summary:

OBJECTIVES: Primary - Determine the maximum tolerated dose of CEP-701 in pediatric patients with recurrent or refractory high-risk neuroblastoma. - Determine the dose-limiting toxicity of this drug in these patients. - Determine the pharmacokinetic behavior of this drug in these patients. Secondary - Determine the degree of TrkB tyrosine kinase inhibition activity present in the serum of patients treated with this drug. - Correlate the degree of TrkB tyrosine kinase inhibition activity in these patients with dose level, pharmacokinetics, and antitumor activity data of this drug. - Determine the antitumor activity of this drug in these patients. OUTLINE: This is an open-label, dose-escalation, multicenter study. Patients receive oral CEP-701 twice daily* on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. NOTE: *On day 1 of course 1 only, patients receive oral CEP-701 once instead of twice. Cohorts of 3-6 patients receive escalating doses of CEP-701 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, the dose level is expanded up to 9 patients. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.


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

Study is Available At:

Original ID:




Secondary ID:


Study Acronym:

Brief Title:

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

Official Title:

A Phase I Study Of CEP-701 In Patients With Refractory Neuroblastoma (IND # 67,722)

Overall Status:


Study Phase:

Phase 1



Minimum Age:


Maximum Age:

30 Years

Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

New Approaches to Neuroblastoma Therapy Consortium

Oversight Authority:

United States: Food and Drug Administration

Reasons Why Stopped:

Study Type:


Study Design:

Endpoint Classification: Safety/Efficacy Study, In

Number of Arms:


Number of Groups:


Total Enrollment:


Enrollment Type:


Overall Contact Information

Official Name:John M. Maris, MD
Principal Investigator
Children's Hospital of Philadelphia

Study Dates

Start Date:August 2003
Completion Date:February 2011
Completion Type:Actual
Primary Completion Date:September 2009
Primary Completion Type:Actual
Verification Date:August 2014
Last Changed Date:August 28, 2014
First Received Date:June 10, 2004

Study Outcomes

Outcome Type:Secondary Outcome
Measure:To define the antitumor activity of CEP-701, within the confines of a Phase I study.
Time Frame:Evaluation at end of courses 1, 2, 4 and then every 4 courses until patient goes off therapy.
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:To determine the degree of TrkB tyrosine kinase inhibition activity present in the serum of patients treated with CEP-701, and correlate these findings with dose level, pharmacokinetic and anti-tumor activity data.
Time Frame:Days 1,5 and 26 of first course only.
Safety Issues:False
Outcome Type:Primary Outcome
Measure:To characterize the pharmacokinetic (PK) behavior of CEP-701 in children with residual or refractory high-risk neuroblastoma.
Time Frame:Days 1,5 and 26 of first course only.
Safety Issues:True
Description:Participation in PK studies is voluntary and not a requirement for study entry.
Outcome Type:Primary Outcome
Measure:To determine dose limiting toxicities (DLTs) of CEP-701 given on this schedule
Time Frame:Within first 28 days of therapy.
Safety Issues:True
Outcome Type:Primary Outcome
Measure:To determine the maximum tolerated dose (MTD) of CEP-701 given on a twice daily chronic administration schedule (two days on , two days off) to children with high risk relapsed or residual neuroblastoma.
Time Frame:Within 28 days of treatment at each dose level.
Safety Issues:True

Study Interventions

Intervention Type:Drug
Description:Given orally twice daily x 5 consecutive days followed by a two day rest. 28 days = 1 treatment course. Courses repeated indefinitely without gap provided patient has recovered course from toxicities and no DLTs. Dose level assigned according to the planned dose escalation schedule.
Other Name:CEP-701

Study Arms

There are no available Study Arms

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:New Approaches to Neuroblastoma Therapy Consortium
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation:Maris J, Minturn J, Evans A, et al.: Phase I trial of the orally bioavailable TRK tyrosine kinase inhibitor CEP-701 in refractory neuroblastoma: a New Approaches to Neuroblastoma Therapy (NANT) study. [Abstract] Pediatr Blood Cancer 45 (4 Suppl 1): A-0.129, 416, 2005.
Reference Type:Results Reference
Citation:Minturn JE, Villablanca J, Yanik GA, et al.: Phase I trial of lestaurtinib for children with refractory neuroblastoma (NB): A New Approach to Neuroblastoma Therapy (NANT) Consortium study. [Abstract] J Clin Oncol 28 (Suppl 15): A-9532, 2010.

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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