Irinotecan Hydrochloride, Temozolomide, and Dinutuximab with or without Eflornithine in Treating Patients with Relapsed or Refractory Neuroblastoma

Active:	Yes
Cancer Type:	Neuroblastoma	NCT ID:	NCT03794349
Trial Phases:	Phase II	Protocol IDs:	ANBL1821 (primary) NCI-2018-03377 ANBL1821
Eligibility:	1 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	Children's Oncology Group
NCI Full Details:	http://clinicaltrials.gov/show/NCT03794349

Summary

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.

Objectives

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.

Treatment Sites in Georgia

Aflac Cancer and Blood Disorders Center of Children’s at Egleston
1405 Clifton Road NE
3rd Floor
Atlanta, GA 30322
404-785-0853
www.choa.org

Curtis and Elizabeth Anderson Cancer Institute at Memorial University Medical Center
4700 Waters Avenue
Savannah, GA 31404
912-350-8913
www.memorialhealth.com/anderson-cancer-institute.aspx

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