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

Official Title

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

Summary:

This phase II trial studies how well irinotecan hydrochloride (irinotecan), temozolomide, and dinutuximab work with or without eflornithine in treating patients with neuroblastoma that has come back or that isn't responding to treatment. Drugs used in chemotherapy, such as irinotecan hydrochloride and temozolomide, work in different ways to stop the growth of tumour 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 tumour 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.

Trial Description

Primary Outcome:

  • Response rate
Secondary Outcome:
  • Progression-free survival (PFS)
  • Overall survival (OS)
  • Incidence of adverse events >= Grade 3 (Regimen B)

PRIMARY OBJECTIVES:

  • To determine whether administration of 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:

  • To compare progression-free survival and overall survival between patients receiving dinutuximab, irinotecan and temozolomide with and without the addition of DFMO.
  • To define the toxicity profile of DFMO administered with dinutuximab, irinotecan and temozolomide.

EXPLORATORY OBJECTIVES:

  • To characterize the immune and cytokine profiles of patients treated with DFMO/chemotherapy/dinutuximab combination and correlate with response to therapy.
  • To evaluate GD2 levels in tumour cells from patient bone marrow samples and correlate with response to therapy.
  • 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 17 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 21 of cycle 1 and days 1-21 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 17 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.

View this trial on ClinicalTrials.gov

Interested in this trial?

Print this page and take it to your doctor to discuss your eligibilty and treatment options. Only your doctor can refer you to a clinical trial.

Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society