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Fenretinide in Treating Children With Recurrent or Resistant Neuroblastoma

Primary Purpose

Recurrent Neuroblastoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
fenretinide
pharmacological study
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Neuroblastoma

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis of recurrent or resistant/refractory high-risk neuroblastoma by one or both of the following: Histological confirmation Demonstration of tumor cells in bone marrow with increased urinary catecholamines Stratum I: At least 1 unidimensionally measurable lesion* At least 20 mm by MRI and/or CT scan OR at least 10 mm by spiral CT scan Stratum II: Meets one or both of the following criteria: At least 1 site with positive uptake on meta-iodobenzylguanidine (MIBG) I 123 scan Tumor in bilateral bone marrow aspirate/biopsy by routine morphology (no NSE staining only) Stratum III: At least 5 tumor cells/10^6 mononuclear cells in the bone marrow by immunocytology only (on 2 successive bone marrows performed from 1 day to 4 weeks apart) Patients in first response (i.e., patients with persistent tumor at end of frontline therapy, but who have never had disease relapse or progression) must have histological* or morphological (by bone marrow) confirmation** of viable tumor on CT scan, MRI, or MIBG scan after completion of myeloablative therapy (for strata I and II) No catecholamine elevation only Performance status - 0-2 At least 2 months Hemoglobin greater than 7.5 g/dL (transfusion allowed) Bilirubin no greater than 1.5 times normal SGPT and SGOT less than 2.5 times normal Creatinine normal for age No hematuria or proteinuria greater than 1+ on urinalysis Calcium less than 11.6 mg/dL Triglycerides less than 300 mg/dL Not pregnant Negative pregnancy test Fertile patients must use effective contraception No seizure disorders unless on anticonvulsants and well controlled No skin toxicity greater than grade 1 Must be able to consume entire intact study capsule in the dosage prescribed for body surface area Recovered from prior immunotherapy At least 7 days since prior anticancer biologic therapy At least 2 days since prior growth factors Prior autologous stem cell transplantation allowed No prior allogeneic stem cell transplantation No concurrent immunomodulating agents At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered No concurrent anticancer chemotherapy No concurrent steroids Recovered from prior radiotherapy At least 4 weeks since prior radiotherapy to target lesion Prior radiotherapy to non target lesions allowed No concurrent radiotherapy to sole measurable lesion for symptom relief Concurrent palliative radiotherapy to non target or localized painful lesions allowed Prior tretinoin or isotretinoin allowed At least 2 weeks since other prior retinoids No prior fenretinide No concurrent supplemental oral or IV vitamin A, ascorbic acid, or vitamin E (except if contained in routine total parenteral nutrition [TPN] vitamin supplements) No concurrent drugs suspected of causing pseudotumor cerebri (e.g., tetracycline, nalidixic acid, nitrofurantoin, phenytoin, sulfonamides, lithium, amiodarone, or vitamin A [except as part of routine TPN supplements]) No other concurrent anticancer agents

Sites / Locations

  • Children's Oncology Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (fenretinide)

Arm Description

Patients receive oral fenretinide 3 times daily (or 2 times daily if over 18 years of age) on days 1-7. Treatment repeats every 3 weeks for up to 30 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Response rate
A responder is defined to be a patient who achieves a best overall response of complete response (CR), very good partial response (VGPR) or partial response (PR).
Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Assessed via a descriptive tabulation of the toxicity rates, overall and by stratum.

Secondary Outcome Measures

Levels of fenretinide
Assessed via descriptive analysis of the steady state levels of fenretinide overall and by stratum
Plasma retinol levels
Assessed via descriptive analysis of the plasma retinol levels overall and by stratum.
Minimal residual disease (MRD) (Stratum 3)
Assessed by descriptive calculation of the proportion of responders.

Full Information

First Posted
January 27, 2003
Last Updated
October 7, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00053326
Brief Title
Fenretinide in Treating Children With Recurrent or Resistant Neuroblastoma
Official Title
A Phase II Study of Fenretinide (NSC# 374551, IND# 40294) in Children With Recurrent/Resistant High Risk Neuroblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
May 2003 (undefined)
Primary Completion Date
March 2006 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase II trial is studying how well fenretinide works in treating children with recurrent or resistant neuroblastoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
Detailed Description
OBJECTIVES: Determine the response rate in pediatric patients with recurrent or resistant high-risk neuroblastoma treated with fenretinide. Determine the toxic effects of this drug in these patients. Determine the proportion of patients with disease detected only by bone marrow immunocytology, who clear all evidence of disease during treatment with this drug. Determine minimal residual disease response by marrow and meta-iodobenzylguanidine (MIBG) I 123 scan in patients treated with this drug. OUTLINE: Patients are stratified according to presence of measurable disease on CT scan/MRI (yes vs no). A third stratum of patients with tumor cells in bone marrow by immunocytology only is enrolled but is not evaluated for response. Patients receive oral fenretinide 3 times daily (or 2 times daily if over 18 years of age) on days 1-7. Treatment repeats every 3 weeks for up to 30 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum III who fail to achieve a complete response after 8 courses of therapy are removed from study. Patients are followed monthly until blood counts and visual acuity are stable or normalized and then every 6 months for 2 years and annually for 3 years. PROJECTED ACCRUAL: A total of 70 patients (25 each for strata I and II, 20 for stratum III) will be accrued for this study within 1-2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Neuroblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (fenretinide)
Arm Type
Experimental
Arm Description
Patients receive oral fenretinide 3 times daily (or 2 times daily if over 18 years of age) on days 1-7. Treatment repeats every 3 weeks for up to 30 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
fenretinide
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
pharmacological study
Intervention Description
Optional correlative studies
Primary Outcome Measure Information:
Title
Response rate
Description
A responder is defined to be a patient who achieves a best overall response of complete response (CR), very good partial response (VGPR) or partial response (PR).
Time Frame
Up to 8 courses of therapy
Title
Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Description
Assessed via a descriptive tabulation of the toxicity rates, overall and by stratum.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Levels of fenretinide
Description
Assessed via descriptive analysis of the steady state levels of fenretinide overall and by stratum
Time Frame
At baseline and during courses 1, 2, and 5
Title
Plasma retinol levels
Description
Assessed via descriptive analysis of the plasma retinol levels overall and by stratum.
Time Frame
At baseline and during courses 1, 2, and 5
Title
Minimal residual disease (MRD) (Stratum 3)
Description
Assessed by descriptive calculation of the proportion of responders.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of recurrent or resistant/refractory high-risk neuroblastoma by one or both of the following: Histological confirmation Demonstration of tumor cells in bone marrow with increased urinary catecholamines Stratum I: At least 1 unidimensionally measurable lesion* At least 20 mm by MRI and/or CT scan OR at least 10 mm by spiral CT scan Stratum II: Meets one or both of the following criteria: At least 1 site with positive uptake on meta-iodobenzylguanidine (MIBG) I 123 scan Tumor in bilateral bone marrow aspirate/biopsy by routine morphology (no NSE staining only) Stratum III: At least 5 tumor cells/10^6 mononuclear cells in the bone marrow by immunocytology only (on 2 successive bone marrows performed from 1 day to 4 weeks apart) Patients in first response (i.e., patients with persistent tumor at end of frontline therapy, but who have never had disease relapse or progression) must have histological* or morphological (by bone marrow) confirmation** of viable tumor on CT scan, MRI, or MIBG scan after completion of myeloablative therapy (for strata I and II) No catecholamine elevation only Performance status - 0-2 At least 2 months Hemoglobin greater than 7.5 g/dL (transfusion allowed) Bilirubin no greater than 1.5 times normal SGPT and SGOT less than 2.5 times normal Creatinine normal for age No hematuria or proteinuria greater than 1+ on urinalysis Calcium less than 11.6 mg/dL Triglycerides less than 300 mg/dL Not pregnant Negative pregnancy test Fertile patients must use effective contraception No seizure disorders unless on anticonvulsants and well controlled No skin toxicity greater than grade 1 Must be able to consume entire intact study capsule in the dosage prescribed for body surface area Recovered from prior immunotherapy At least 7 days since prior anticancer biologic therapy At least 2 days since prior growth factors Prior autologous stem cell transplantation allowed No prior allogeneic stem cell transplantation No concurrent immunomodulating agents At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered No concurrent anticancer chemotherapy No concurrent steroids Recovered from prior radiotherapy At least 4 weeks since prior radiotherapy to target lesion Prior radiotherapy to non target lesions allowed No concurrent radiotherapy to sole measurable lesion for symptom relief Concurrent palliative radiotherapy to non target or localized painful lesions allowed Prior tretinoin or isotretinoin allowed At least 2 weeks since other prior retinoids No prior fenretinide No concurrent supplemental oral or IV vitamin A, ascorbic acid, or vitamin E (except if contained in routine total parenteral nutrition [TPN] vitamin supplements) No concurrent drugs suspected of causing pseudotumor cerebri (e.g., tetracycline, nalidixic acid, nitrofurantoin, phenytoin, sulfonamides, lithium, amiodarone, or vitamin A [except as part of routine TPN supplements]) No other concurrent anticancer agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Judith Villablanca
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Oncology Group
City
Arcadia
State/Province
California
ZIP/Postal Code
91006-3776
Country
United States

12. IPD Sharing Statement

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Fenretinide in Treating Children With Recurrent or Resistant Neuroblastoma

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