Symptoms and General Pathology

All Conditions

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Rare Diseases

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Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

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All Drugs and Chemicals

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Irinotecan

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Antibodies, Monoclonal

Molgramostim

Sargramostim

Temozolomide

Camptothecin

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Eflornithine

Dinutuximab

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunologic Factors

Antiprotozoal Agents

Antiparasitic Agents

Ornithine

Patients receive temozolomide PO, via NG, or G tube on days 1-5, irinotecan hydrochloride IV over 90 minutes on days 1-5, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim SC or IV over 2 hours on days 6-12 of a 21-day cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients receive eflornithine PO, via NG, or G tube on days -6 to 7 and days 15-21 of cycle 1 and days 1-7 and 15-21 of subsequent cycles, temozolomide PO, via NG, or G tube on days 1-5, irinotecan hydrochloride IV over 90 minutes on days 1-5, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim SC or IV over 2 hours on days 6-12. Treatment duration is 28 days for cycle 1 and then every 21 days in subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Eflornithine Hydrochloride

Irinotecan Hydrochloride

Margaret E Macy

This phase II trial studies how well irinotecan hydrochloride, temozolomide, and dinutuximab work with or without eflornithine in treating patients with neuroblastoma that has come back (relapsed) or that isn't responding to treatment (refractory). Drugs used in chemotherapy, such as irinotecan hydrochloride and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as dinutuximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Eflornithine blocks the production of chemicals called polyamines that are important in the growth of cancer cells. Giving eflornithine with irinotecan hydrochloride, temozolomide, and dinutuximab, may work better in treating patients with relapsed or refractory neuroblastoma.

PRIMARY OBJECTIVE:

I. To determine whether administration of eflornithine hydrochloride (eflornithine \[DFMO\]) in combination with dinutuximab, irinotecan hydrochloride (irinotecan) and temozolomide results in an improved response rate compared to dinutuximab, irinotecan and temozolomide in patients with relapsed or refractory neuroblastoma and therefore is a therapeutic regimen worthy of further testing in patients with newly-diagnosed high-risk neuroblastoma.

SECONDARY OBJECTIVES:

I. To compare progression-free survival and overall survival between patients receiving dinutuximab, irinotecan and temozolomide with and without the addition of DFMO.

II. To define the toxicity profile of DFMO administered with dinutuximab, irinotecan and temozolomide.

EXPLORATORY OBJECTIVES:

I. To characterize the immune and cytokine profiles of patients treated with DFMO/chemotherapy/dinutuximab combination and correlate with response to therapy.

II. To evaluate GD2 levels in tumor cells from patient bone marrow samples and correlate with response to therapy.

III. To explore whether the addition of DFMO to the dinutuximab and chemotherapy backbone affects pain as determined by patient report and opiate usage.

OUTLINE: Patients are randomized to 1 of 2 regimens.

REGIMEN A: Patients receive temozolomide orally (PO), via nasogastric (NG), or gastric (G) tube on days 1-5, irinotecan hydrochloride intravenously (IV) over 90 minutes on days 1-5, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim subcutaneously (SC) or IV over 2 hours on days 6-12 of a 21-day cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

REGIMEN B: Patients receive eflornithine PO, via NG, or G tube on days -6 to 7 and days 15-21 of cycle 1 and days 1-7 and 15-21 of subsequent cycles, temozolomide PO, via NG, or G tube on days 1-5, irinotecan hydrochloride intravenously (IV) over 90 minutes on days 1-5, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim SC or IV over 2 hours on days 6-12. Treatment lasts 28 days for cycle 1 and then every 21 days for subsequent cycles up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and periodically for 5 years.

Irinotecan Hydrochloride, Temozolomide, and Dinutuximab With or Without Eflornithine in Treating Patients With Relapsed or Refractory Neuroblastoma

A Phase 2 Randomized Study of Irinotecan/Temozolomide/Dinutuximab With or Without Eflornithine (DFMO) in Children With Relapsed, Refractory or Progressive Neuroblastoma

Will be assessed by exploring the relationship between response (responder versus \[vs.\] non-responder) after 6 cycles on Regimen B with serum cytokine levels (IL1, IL6, tumor necrosis factor \[TNF\]-alpha, IFN-gamma, etc.), tumor resident immune cells (natural killer \[NK\] cells, tumor-associated macrophages \[TAMS\], tumor infiltrating lymphocyte \[TILS\]), and critical immune cell suppressing proteins (B7H3, PDL-1) using Fisher's exact test for categorical and Wilcoxon rank-sum test for continuous factors.

Will be correlated with response (responder vs. non-responder) after 6 cycles using Fisher's exact test for categorical and the Wilcoxon rank-sum test for continuous factors.

The occurrence of pain on each regimen as reported by patient report and opiate use will be descriptively summarized. Descriptive and summary statistics will be used to describe the scores from the Faces Pain Scale-Revised during the dinutuximab infusion and on day 1 with irinotecan and temozolomide alone for each arm separately. Confidence intervals will be constructed for the mean and frequency estimates. The day 1 patient reported outcome data are expected to be similar between the 2 regimens, while differences during or after completion of treatment may be observed.

Responders are defined as patients who achieve a \>= minor response (MR) per the International Neuroblastoma Response Criteria (INRC) as their best overall response by the end of 6 cycles. The response rate to treatment will be calculated among all eligible patients, including placement of a 95% confidence interval on the response rate.

Kaplan-Meier method will be used to estimate progression-free survival (PFS). PFS time will be calculated from the time of randomization to the occurrence of relapse, progressive disease, or death. Patients without a PFS event will be censored at the time of last follow-up.

Kaplan-Meier method will be used to estimate overall survival (OS). OS time will be calculated from the time of randomization to the occurrence of death. Patients still alive will be censored at the time of last follow-up.

The percentage of patients on Regimen B with at least one Grade 3 or higher toxicity will be calculated, assessed with Common Terminology Criteria for Adverse Events version 5.0.

National Cancer Institute (NCI)

Children's Oncology Group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Irinotecan Hydrochloride, Temozolomide, and Dinutuximab With or Without Eflornithine in Treating Patients With Relapsed or Refractory Neuroblastoma	NCT03794349	High Risk Neuro... Recurrent Neuro... Refractory Neur...	Dinutuximab Eflornithine Hy... Irinotecan Hydr... Sargramostim Temozolomide	1 Year -	Children's Oncology Group
Irinotecan Hydrochloride, Temozolomide, and Dinutuximab With or Without Eflornithine in Treating Patients With Relapsed or Refractory Neuroblastoma	NCT03794349	High Risk Neuro... Recurrent Neuro... Refractory Neur...	Dinutuximab Eflornithine Hy... Irinotecan Hydr... Sargramostim Temozolomide	1 Year -	Children's Oncology Group

Spots Global Cancer Trial Database for eflornithine hydrochloride