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NCT01767194

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

Completed Phase 2 Results posted Last updated 24 October 2022
What this trial tests

Phase 2 trial testing Dinutuximab in Ganglioneuroblastoma in 73 participants. Completed in 30 September 2022.

Timeline
12 February 2013
Primary endpoint
30 June 2018
30 September 2022

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment73
Start date12 February 2013
Primary completion30 June 2018
Estimated completion30 September 2022
Sites157 locations across New Zealand, Canada, Puerto Rico, Australia, United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Eligibility, any sex, with Ganglioneuroblastoma or Recurrent Neuroblastoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Randomized Patients Who Are Responders Primary · Up to the first 6 cycles of treatment

The percentage of patients who are responders will be tabulated, including a 95% confidence interval on the response rate. Responders are defined as patients who achieve a best overall response of complete response (CR), very good partial response (VGPR), or partial response (PR) per the International Neuroblastoma Response Criteria (INRC). Per INRC: CR= Disappearance of all target lesions. No evidence of tumor at any site; VGPR= \>90% decrease of the disease measurement for CT/MRI target lesions. All pre-existing bone lesions with CR by MIBG; MIBG scan can be stable disease (SD) or CR in soft

GroupValue95% CI
Arm I (Temozolomide, Irinotecan Hydrochloride, Temsirolimus)5.60.0 – 16.1
Arm II (Temozolomide, Irinotecan Hydrochloride, Dinutuximab)52.929.2 – 76.7
Percentage of Patients in the Dinutuximab Arm Who Are Responders Primary · Up to the first 6 cycles of treatment

Percentage of patients who are responders to therapy with dinutuximab will be tabulated, including a 95% confidence interval on the response rate. Responders are defined as patients who achieve a best overall response of complete response (CR), very good partial response (VGPR), or partial response (PR) per the International Neuroblastoma Response Criteria (INRC). Per INRC: CR= Disappearance of all target lesions. No evidence of tumor at any site; VGPR= \>90% decrease of disease measurement for CT/MRI target lesions. All pre-existing bone lesions with CR by MIBG; MIBG scan can be stable diseas

GroupValue95% CI
Arm II (Temozolomide, Irinotecan Hydrochloride, Dinutuximab)41.228.2 – 54.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Through completion of protocol therapy, up to approximately 1 year.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm I (Temozolomide, Irinotecan Hydrochloride, Temsirolimus)
Serious: 5/18 (28%)
Deaths: 12/18
Arm II (Temozolomide, Irinotecan Hydrochloride, Dinutuximab)
Serious: 18/51 (35%)
Deaths: 15/51

Serious adverse events (47 terms)

ReactionSystemArm I (Temozolomide, Irino…Arm II (Temozolomide, Irin…
Neutrophil count decreasedInvestigations
HypoxiaRespiratory, thoracic and mediastinal disorders
AnemiaBlood and lymphatic system disorders
Aspartate aminotransferase increasedInvestigations
DehydrationMetabolism and nutrition disorders
DiarrheaGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
WheezingRespiratory, thoracic and mediastinal disorders
White blood cell decreasedInvestigations
Alanine aminotransferase increasedInvestigations
Allergic reactionImmune system disorders
AnaphylaxisImmune system disorders
AnorexiaMetabolism and nutrition disorders
BACTEREMIA - LINE INFECTIONSInfections and infestations
BLOODInfections and infestations
BronchospasmRespiratory, thoracic and mediastinal disorders
Creatinine increasedInvestigations
Death NOSGeneral disorders
Depressed level of consciousnessNervous system disorders
FeverGeneral disorders
GGT increasedInvestigations
HeadacheNervous system disorders
Hearing impairedEar and labyrinth disorders
Other adverse events (65 terms — click to expand)

ReactionSystemArm I (Temozolomide, Irino…Arm II (Temozolomide, Irin…
White blood cell decreasedInvestigations
Lymphocyte count decreasedInvestigations
Neutrophil count decreasedInvestigations
AnemiaBlood and lymphatic system disorders
FeverGeneral disorders
PainGeneral disorders
HypokalemiaMetabolism and nutrition disorders
Alanine aminotransferase increasedInvestigations
DiarrheaGastrointestinal disorders
HyponatremiaMetabolism and nutrition disorders
Platelet count decreasedInvestigations
HypotensionVascular disorders
VomitingGastrointestinal disorders
HypocalcemiaMetabolism and nutrition disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
HyperglycemiaMetabolism and nutrition disorders
Urinary tract infectionInfections and infestations
AnorexiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
Capillary leak syndromeVascular disorders
GGT increasedInvestigations
HyperkalemiaMetabolism and nutrition disorders
IrritabilityPsychiatric disorders
Mucositis oralGastrointestinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Activated partial thromboplastin time prolongedInvestigations
Allergic reactionImmune system disorders
Back painMusculoskeletal and connective tissue disorders
BACTEREMIAInfections and infestations
BLOODInfections and infestations
BLOOD - STAPHYLOCOCCUS EPIDERMIDIS ISOLATED.Infections and infestations
BLOOD - STAPHYLOCOCCUS HOMINIS ISOLATESInfections and infestations
Blood bilirubin increasedInvestigations
Blurred visionEye disorders
Cardiac arrestCardiac disorders
CENTRAL LINE INFECTIONInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
DeliriumPsychiatric disorders

Most-reported serious reactions: Neutrophil count decreased, Hypoxia, Anemia, Aspartate aminotransferase increased, Dehydration, Diarrhea, Dyspnea, Febrile neutropenia.

Data from ClinicalTrials.gov NCT01767194 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Advances in Risk Classification and Treatment Strategies for Neuroblastoma.
    Pinto NR, Applebaum MA, Volchenboum SL, Matthay KK, et al · · 2015 · cited 676× · PMID 26304901 · DOI 10.1200/jco.2014.59.4648
  2. Molecular targeting therapies for neuroblastoma: Progress and challenges.
    Zafar A, Wang W, Liu G, Wang X, et al · · 2021 · cited 291× · PMID 33155698 · DOI 10.1002/med.21750
  3. Targeting cytokine and chemokine signaling pathways for cancer therapy.
    Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
  4. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial.
    Mody R, Naranjo A, Van Ryn C, Yu AL, et al · · 2017 · cited 226× · PMID 28549783 · DOI 10.1016/s1470-2045(17)30355-8
  5. Anti-GD2 immunotherapy for neuroblastoma.
    Sait S, Modak S. · · 2017 · cited 155× · PMID 28780888 · DOI 10.1080/14737140.2017.1364995
  6. Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group.
    Mody R, Yu AL, Naranjo A, Zhang FF, et al · · 2020 · cited 145× · PMID 32343642 · DOI 10.1200/jco.20.00203
  7. Neuroblastoma Origin and Therapeutic Targets for Immunotherapy.
    Kholodenko IV, Kalinovsky DV, Doronin II, Deyev SM, et al · · 2018 · cited 122× · PMID 30116755 · DOI 10.1155/2018/7394268
  8. New strategies in neuroblastoma: Therapeutic targeting of MYCN and ALK.
    Barone G, Anderson J, Pearson AD, Petrie K, et al · · 2013 · cited 101× · PMID 23965898 · DOI 10.1158/1078-0432.ccr-13-0680

Verify or expand the search:

Other trials of Dinutuximab

Trials testing the same drug.

Other recruiting trials for Ganglioneuroblastoma

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

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