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Irinotecan and Temozolomide in Treating Young Patients With Recurrent Neuroblastoma

Phase 2
Completed
Conditions
Neuroblastoma
Interventions
Registration Number
NCT00311584
Lead Sponsor
Children's Oncology Group
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving irinotecan together with temozolomide works in treating young patients with recurrent neuroblastoma.

Detailed Description

OBJECTIVES:

Primary

* Determine the response rate in pediatric patients with relapsed neuroblastoma (NB) treated with irinotecan hydrochloride and temozolomide.

* Determine the toxicities associated with irinotecan and temozolomide in patients treated with this regimen.

Secondary

* Evaluate the impact of p53 loss of function on response rate and event-free survival from start of relapse therapy.

* Collect data for ongoing analyses of UGT1A1 polymorphisms in these patients.

* Collect and bank serum and nucleic acid specimen to facilitate future biomarker studies.

* Evaluate the feasibility of collecting blood samples on a group wide basis for assessment of changes in circulating markers of angiogenesis.

* Assess, preliminarily, the effects of irinotecan hydrochloride and temozolomide on circulating markers of angiogenesis.

OUTLINE: This is a multicenter study.

Patients are stratified according to disease status (measurable disease \[measured by conventional CT scan and/or MRI\] vs evaluable disease \[tumor detected by conventional morphologic analysis of bone marrow aspirate/biopsy AND/OR abnormal uptake at ≥ 1 site on MIBG scan\]).

Patients receive irinotecan hydrochloride IV over 1 hour on days 1-5 and 8-12 and oral temozolomide on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
59
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Disease measurable by CT or MRI scan (Irinotecan/Temozolomide)temozolomideMeasurable by CT scan (Computed Tomography) or MRI scan (Magnetic Resonance Imaging). Patients receive irinotecan hydrochloride IV (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Disease measurable by CT or MRI scan (Irinotecan/Temozolomide)irinotecan hydrochlorideMeasurable by CT scan (Computed Tomography) or MRI scan (Magnetic Resonance Imaging). Patients receive irinotecan hydrochloride IV (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Disease eval by bone marrow or MIBG (Irinotecan/Temozolomide)irinotecan hydrochlorideEvaluation by bone marrow or MIBG scan (metaiodobenzylguanidine scan, a radiopharmaceutical). Patients receive irinotecan hydrochloride IV (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Disease eval by bone marrow or MIBG (Irinotecan/Temozolomide)temozolomideEvaluation by bone marrow or MIBG scan (metaiodobenzylguanidine scan, a radiopharmaceutical). Patients receive irinotecan hydrochloride IV (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Overall Response - Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)up to 6 courses of therapy, or about 6 months

The patient's best overall response obtained during Reporting Periods 1 and 2 will be scored as "best response". Patients enrolled on Stratum 1 with bone marrow disease, a responder has no tumor cells detectable by routine morphology on 2 subsequent bilateral bone marrow aspirates and biopsies done at least 3 weeks apart. For patients enrolled on stratum 1 with MIBG only disease, response will be assessed using the Curie scale. Patients who have complete resolution of all MIBG positive lesions (CR) or resolution of at least one MIBG positive lesion with persistence of other lesions (PR) will be considered responders. For Stratum 2 a responder is defined to be a patient who achieves a best overall response of CR, VGPR or PR from CT/MRI scans from central review using (RECIST) Response Evaluation Criteria in Solid Tumor. A responder is defined to be a patient who achieves a best overall response of CR (Complete Response), VGPR (Very Good Partial Response) or PR (Partial Response).

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (127)

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

🇺🇸

Birmingham, Alabama, United States

Arizona Cancer Center at University of Arizona Health Sciences Center

🇺🇸

Tucson, Arizona, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Southern California Permanente Medical Group

🇺🇸

Downey, California, United States

Loma Linda University Cancer Institute at Loma Linda University Medical Center

🇺🇸

Loma Linda, California, United States

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital

🇺🇸

Long Beach, California, United States

Childrens Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Children's Hospital Central California

🇺🇸

Madera, California, United States

Children's Hospital and Research Center Oakland

🇺🇸

Oakland, California, United States

Children's Hospital of Orange County

🇺🇸

Orange, California, United States

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Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
🇺🇸Birmingham, Alabama, United States
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