Fenretinide in Treating Children With Recurrent or Resistant Neuroblastoma

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Recurrent Neuroblastoma

Treatments

Drug: fenretinide

Other: pharmacological study

Study type

Interventional

Funder types

NIH

Identifiers

NCT00053326

COG-ANBL0321

ADVL0024 (Other Identifier)

ANBL0321 (Other Identifier)

COG-A0996

U10CA098543 (U.S. NIH Grant/Contract)

NCI-2012-01802 (Registry Identifier)

CDR0000269408

COG-ADVL0024

Details and patient eligibility

About

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.

Full 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.

Enrollment

70 estimated patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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