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

NCT ID: NCT00084422

Last Updated: 2023-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-08-31
• Study Completion Date: 2011-02-28

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.

Detailed Description

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.

Conditions

Neuroblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Group

Group Type: EXPERIMENTAL

lestaurtinib

Intervention Type: 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.

Interventions

lestaurtinib

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.

Intervention Type: DRUG

Other Intervention Names

CEP-701

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

New Approaches to Neuroblastoma Therapy Consortium

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John M. Maris, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Garrett M. Brodeur, MD

Role: STUDY_CHAIR

Children's Hospital of Philadelphia

Locations

Childrens Hospital Los Angeles

Los Angeles, California, United States

Lucille Salter Packer Children's Hospital, Stanford University

Palo Alto, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

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

Atlanta, Georgia, United States

University of Chicago Comer Children's Hospital

Chicago, Illinois, United States

Children's Hospital Boston

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Morgan Stanley Children's Hospital of New York-Presbyterian

New York, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Hospital for Sick Children

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: 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.

Reference Type: RESULT

Other Identifiers

P01CA081403

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NANT-2001-03

Identifier Type: -

Identifier Source: secondary_id

CDR0000363630

Identifier Type: -

Identifier Source: org_study_id