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

NCT00084422 | Completed Phase 1 DMC

• 3 other identifiers: CDR0000363630P01CA081403NANT-2001-03
• Study Type: interventional
• Target: 47
• Locations: 2 countries
• Sites: 12

Brief 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.

Conditions

Neuroblastoma

Keywords

recurrent neuroblastoma

Outcome Measures

Primary Outcomes (3)

• 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.

  Within 28 days of treatment at each dose level.

• To determine dose limiting toxicities (DLTs) of CEP-701 given on this schedule

  Within first 28 days of therapy.

• To characterize the pharmacokinetic (PK) behavior of CEP-701 in children with residual or refractory high-risk neuroblastoma.

  Participation in PK studies is voluntary and not a requirement for study entry.

  Days 1,5 and 26 of first course only.

Secondary Outcomes (2)

• 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.

  Days 1,5 and 26 of first course only.

• To define the antitumor activity of CEP-701, within the confines of a Phase I study.

  Evaluation at end of courses 1, 2, 4 and then every 4 courses until patient goes off therapy.

Study Arms (1)

Single Group

EXPERIMENTAL

Drug: lestaurtinib

Interventions

lestaurtinib DRUG

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.

Also known as: CEP-701

Single Group

Eligibility Criteria

• Age: 1 Day - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• New Approaches to Neuroblastoma Therapy Consortium: lead
• National Cancer Institute (NCI): collaborator

Study Sites (12)

Childrens Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Lucille Salter Packer Children's Hospital, Stanford University

Palo Alto, California, 94305, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

Atlanta, Georgia, 30322, United States

Location

University of Chicago Comer Children's Hospital

Chicago, Illinois, 60637, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Morgan Stanley Children's Hospital of New York-Presbyterian

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (2)

• 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.

  RESULT

• 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.

  RESULT

MeSH Terms

Conditions

Neuroblastoma

Interventions

lestaurtinib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• John M. Maris, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

• Garrett M. Brodeur, MD

  Children's Hospital of Philadelphia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2004
• First Posted: June 11, 2004
• Study Start: August 1, 2003
• Primary Completion: September 1, 2009
• Study Completion: February 1, 2011
• Last Updated: April 10, 2023

Record last verified: 2023-04

Locations

US (11); CA (1)