Clinical Trial: Iobenguane I-131 or Crizotinib and Standard Therapy in Treating Younger Patients With Newly-Diagnosed High-Risk Neuroblastoma or Ganglioneuroblastoma

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or Crizotinib Added to Standard Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma (NBL)

Brief Summary: This partially randomized phase III trial studies iobenguane I-131 or crizotinib and standard therapy in treating younger patients with newly-diagnosed high-risk neuroblastoma or ganglioneuroblastoma. Radioactive drugs, such as iobenguane I-131, may carry radiation directly to tumor cells and not harm normal cells. Crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving iobenguane I-131 or crizotinib and standard therapy may work better in treating younger patients with neuroblastoma or ganglioneuroblastoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine in the context of a randomized trial whether the event-free survival (EFS) of patients with newly diagnosed high-risk neuroblastoma (NBL) is improved with the addition of iobenguane I-131 (131I-MIBG) during Induction, prior to tandem autologous stem cell transplantation (ASCT).

II. To determine whether the addition of crizotinib to standard multimodality therapy for patients with high-risk NBL whose tumors harbor activating point mutations in or amplification of the ALK gene results in superior EFS compared to a contemporaneously treated cohort of patients whose tumors lack these ALK aberrations.

SECONDARY OBJECTIVES:

I. To describe the toxicities associated with treatment for high-risk NBL with and without the addition of 131I-MIBG or crizotinib.

II. To compare EFS and toxicity in patients with newly diagnosed high-risk NBL randomized to treatment with an 131I-MIBG-containing induction prior to either tandem or busulfan/melphalan (BuMel) ASCT.

III. To describe the overall survival (OS) and response rates (evaluated per International Neuroblastoma Response Criteria [INRC] criteria prior to ASCT and prior to post-consolidation therapy) for patients with high-risk neuroblastoma treated with or without 131I-MIBG or crizotinib.

IV. To prospectively evaluate the relationship of response rate per revised International Neuroblastoma Response Criteria (INRC) to EFS and OS in patients with high-risk NBL treated with and without the addition of 131I-MIBG or crizotinib.

TERTIARY OBJECTIVES:

Sponsor: Children's Oncology Group

Current Primary Outcome: EFS rate [ Time Frame: From the time of randomization or assignment to first episode of disease relapse or progression, first occurrence of a second malignancy, or death, assessed for up to 5 years ]

Will be assessed with an intent-to-treat log-rank test comparison of EFS rates. The EFS of patients assigned to the ALK-aberrant crizotinib treatment arm will be compared with an intent-to-treat log-rank test to that of all patients assigned to the ALK wild type portion of the trial, except for those patients randomized to receive 131I-MIBG.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria version 4.0 [ Time Frame: Up to 5 years ]
    Will use chi-squared tests to determine incremental increases in toxicity that result from the addition of crizotinib. Separate comparisons for Induction, Consolidation, post-Consolidation (with immunotherapy and with crizotinib monotherapy), and follow-up phases will be performed. Chi-squared and Wilcoxon rank-sum tests will be used to assess incremental increases in toxicity from the addition of 131I-MIBG.
  • Non-inferiority of 131I-MIBG plus BuMel and 131I-MIBG plus tandem transplant [ Time Frame: Up to 5 years ]
    The 131I-MIBG plus BuMel arm will be compared to the 131I-MIBG plus tandem transplant arm, and success will be declared and the 131I-MIBG plus BuMel arm deemed non-inferior to the 131I-MIBG plus tandem transplant arm if the upper boundary of the two-sided 90% confidence interval for the hazard ratio from a Cox proportional hazards model is less than 1.3.


Original Secondary Outcome: Same as current

Information By: Children's Oncology Group

Dates:
Date Received: April 17, 2017
Date Started: August 2017
Date Completion: March 2022
Last Updated: April 24, 2017
Last Verified: April 2017