Completed

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

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What is being tested

lestaurtinib

Drug
Who is being recruted

Neuroblastoma

Until 30 Years
How is the trial designed

Treatment Study

Phase 1
Interventional
Study Start: August 2003

Summary

Principal SponsorNew Approaches to Neuroblastoma Therapy Consortium
Last updated: April 10, 2023
Sourced from a government-validated database.Claim as a partner
Study start date: August 1, 2003Actual date on which the first participant was enrolled.

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. 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.

Official TitleA Phase I Study Of CEP-701 In Patients With Refractory Neuroblastoma (IND # 67,722) 
Principal SponsorNew Approaches to Neuroblastoma Therapy Consortium
Last updated: April 10, 2023
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
47 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, all participants receive the same treatment. Since there is only one group, there is no need for randomization or assignment to different arms. This type of study is often used to test a new treatment without comparing it to another.

Other Ways to Assign Participants
Randomized allocation
: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.

Non-randomized allocation
: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment
: Participants are split into separate groups, each receiving a different treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled
: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Double-blind
: Neither participants nor researchers know which treatment is given.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Until 30 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Neuroblastoma
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


Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
One single intervention group 

is designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
Study Objectives
Primary Objectives

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


Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 12 locations
Suspended
Childrens Hospital Los AngelesLos Angeles, United StatesSee the location
Suspended
Lucille Salter Packer Children's Hospital, Stanford UniversityPalo Alto, United States
Suspended
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, United States
Suspended
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston CampusAtlanta, United States

Completed12 Study Centers