NCT01767194

Irinotecan Hydrochloride and Temozolomide With Temsirolimus or Dinutuximab in Treating Younger Patients With Refractory or Relapsed Neuroblastoma

A Phase II Randomized Trial of Irinotecan/Temozolomide With Temsirolimus (NSC# 683864) or Chimeric 14.18 Antibody (Ch14.18) (NSC# 764038) in Children With Refractory, Relapsed or Progressive Neuroblastoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 73 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

This randomized phase II trial studies how well irinotecan hydrochloride and temozolomide with temsirolimus or dinutuximab work in treating younger patients with neuroblastoma that has returned or does not respond to treatment. 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. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as dinutuximab, may find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving irinotecan hydrochloride and temozolomide together with temsirolimus or dinutuximab is more effective in treating neuroblastoma.

Detailed description

PRIMARY OBJECTIVES: I. To identify whether temsirolimus or ch14.18 (dinutuximab) is the optimal therapeutic agent to consider for further testing in a future Phase III randomized trial for treatment of newly diagnosed high-risk neuroblastoma. II. To determine the response rate of patients with relapsed, refractory or progressive neuroblastoma following treatment with irinotecan, temozolomide and ch14.18 (dinutuximab) and to compare this with the known response rate of patients treated with irinotecan and temozolomide alone. EXPLORATORY OBJECTIVES: I. To compare the response rates (RR) for patients receiving temsirolimus or ch14.18 (dinutuximab) in combination with irinotecan (irinotecan hydrochloride) and temozolomide. II. To compare the progression free survival (PFS) and overall survival (OS) rates for patients receiving temsirolimus or ch14.18 (dinutuximab) in combination with irinotecan and temozolomide. III. To compare the toxicities associated with temsirolimus or ch14.18 (dinutuximab) when combined with irinotecan and temozolomide in patients with refractory, relapsed or progressive neuroblastoma. IV. To compare the ability to maintain intended dose intensity of all agents when temsirolimus or ch14.18 (dinutuximab) is combined with irinotecan and temozolomide in patients with refractory, relapsed or progressive neuroblastoma. V. To determine the concordance between tumor responses as defined by standard International Neuroblastoma Response Criteria (INRC) versus response per the revised INRC. VI. To study the clinical relevance of naturally occurring anti-glycan antibodies in patients receiving ch14.18 (dinutuximab) antibody. VII. To study the clinical relevance of natural killer (NK) receptor natural cytotoxicity triggering receptor 3 (NKp30) isoforms in patients receiving ch14.18 (dinutuximab) antibody or temsirolimus. VIII. To study the association between host factors and response to irinotecan, temozolomide and ch14.18 (dinutuximab). IX. To characterize the tumor immune-microenvironment (gene expression; immune effector cells, activities and signaling molecules; immune target expression) following treatment with irinotecan, temozolomide and ch14.18 (dinutuximab). X. To study the association between changes in the tumor immune-microenvironment (gene expression; immune effector cells, activities and signaling molecules; immune target expression) with response following treatment with irinotecan, temozolomide and ch14.18 (dinutuximab). XI. To study the association between tumor genomic and transcriptomic aberrations as well as levels of circulating ganglioside (GD2) with response to irinotecan, temozolomide and ch14.18 (dinutuximab). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I (CLOSED TO ACCRUAL 06/17/2016): Patients receive temozolomide orally (PO) on days 1-5, irinotecan hydrochloride intravenously (IV) over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8. ARM II: Patients receive temozolomide PO on days 1-5, irinotecan hydrochloride 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. In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Conditions

• Ganglioneuroblastoma
• Recurrent Neuroblastoma

Interventions

Type	Name	Description
BIOLOGICAL	Dinutuximab	Given IV
DRUG	Irinotecan Hydrochloride	Given IV
OTHER	Laboratory Biomarker Analysis	Optional correlative studies
BIOLOGICAL	Sargramostim	Given SC or IV
DRUG	Temozolomide	Given PO
DRUG	Temsirolimus	Given IV

Timeline

• Start date: 2013-02-12
• Primary completion: 2018-06-30
• Completion: 2022-09-30
• First posted: 2013-01-14
• Last updated: 2022-10-24
• Results posted: 2019-11-18

Locations

157 sites across 5 countries: United States, Australia, Canada, New Zealand, Puerto Rico