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

Completed · Phase 2

Conditions studied: Ganglioneuroblastoma, Recurrent Neuroblastoma

In brief

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.

Key facts

Study ID

NCT01767194

Run by

National Cancer Institute (NCI)

People needed

73

Starts

2013-02-12

Expected to finish

2022-09-30

Last updated by the study team

2022-10-24

Who can join

Age: any. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have had histologic verification of neuroblastoma or ganglioneuroblastoma or demonstration of neuroblastoma cells in the bone marrow with elevated urinary catecholamines (i.e., > 2 x upper limit of normal [ULN]), at the time of initial diagnosis
• For the purposes of this study, aggressive multidrug chemotherapy is defined as chemotherapy including 2 or more agents that must include an alkylating agent and a platinum-containing compound; patients must have ONE of the following:
• First episode of recurrent disease following completion of aggressive multi-drug frontline therapy
• First episode of progressive disease during aggressive multi-drug frontline therapy
• Primary resistant/refractory disease (less than partial response by INRC) detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include A3973, ANBL0532, ANBL09P1, etc.)
• Patients must have at least ONE of the following:
• Measurable tumor on magnetic resonance imaging (MRI), computed tomography (CT) scan obtained within 3 weeks prior to study entry; measurable is defined as >= 10 mm in at least one dimension on spiral/helical CT that is metaiodobenzylguanidine (MIBG) avid or demonstrates increased fludeoxyglucose (FDG) uptake on positron emission tomography (PET) scan
• MIBG scan obtained within 3 weeks prior to study entry with positive uptake at a minimum of one site; this site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction
• Patients with resistant/refractory soft tissue disease that is not MIBG avid or does not demonstrate increased FDG uptake on PET scan must undergo biopsy to document the presence of viable neuroblastoma; biopsy is not required for patients who have new site of soft tissue disease (radiographic evidence of disease progression) regardless of whether progression occurs while receiving therapy or after completion of therapy
• Note: Patients with elevated catecholamines (i.e., > 2 x ULN) only or bone marrow disease only are NOT eligible for this study
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
• Patients must have received frontline therapy (including surgery, chemotherapy, autologous stem cell transplant [SCT] +/- MIBG, immunotherapy, radiotherapy, and retinoids) but may NOT have received second line chemotherapy for resistant/refractory, relapsed disease or progressive disease
• At least 14 days must have elapsed since completion of myelosuppressive therapy
• At least 7 days must have elapsed since the completion of therapy with a non-myelosuppressive biologic agent or retinoid
• No interim time prior to study entry is required following prior radiation therapy (RT) for non-target lesions; however, patients must not have received radiation for a minimum of 4 weeks prior to study entry at the site of any lesion that will be identified as a target lesion to measure tumor response; lesions that have been previously radiated cannot be used as target lesions unless there is radiographic evidence of progression at the site following radiation or a biopsy done following radiation shows viable neuroblastoma; palliative radiation is allowed to sites that will not be used to measure response during this study
• Patients are eligible >= 6 weeks after autologous stem cell transplants or stem cell infusions as long as hematologic and other eligibility criteria have been met
• Patients are eligible >= 6 weeks after therapeutic 131I-MIBG provided that all other eligibility criteria are met
• Subjects who have previously received anti-GD2 monoclonal antibodies for biologic therapy or for tumor imaging are eligible unless they have had progressive disease while receiving prior anti-GD2 therapy; subjects who have received autologous marrow infusions or autologous stem cell infusions that were purged using monoclonal antibody linked to beads, but no other form of anti-GD2 monoclonal antibody, are eligible
• Patients must not have received long-acting myeloid growth factors (e.g., Neulasta) within 14 days of entry on this study; seven days must have elapsed since administration of a short acting myeloid growth factor
• Peripheral absolute neutrophil count (ANC) >= 750/uL
• Platelet count >= 75,000/uL (transfusion independent)
• Patients known to have bone marrow involvement with neuroblastoma are eligible provided that minimum ANC and platelet count criteria are met but are not evaluable for hematological toxicity
• Creatinine clearance or estimated radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m\^2 or
• A serum creatinine =< upper limit of normal (ULN) based on age/gender as follows:
• Age 1 month to < 6 months: 0.4 for males, 0.4 for females

You may not qualify if…

• Men and women of childbearing potential and their partners must agree to use adequate contraception while enrolled on this study; based on the established teratogenic potential of alkylating agents, pregnant women will be excluded from this study; female patients who are lactating must agree to stop breastfeeding or will otherwise be excluded from this study; females of childbearing potential must have a negative pregnancy test to be eligible for this study
• Patients with elevated catecholamines (i.e., > 2 x ULN) only or bone marrow disease only are NOT eligible for this study
• Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment; patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study are ineligible; the only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration in order to avoid allergic transfusion reactions; the use of conventional doses of inhaled steroids for the treatment of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal insufficiency
• Patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, valproic acid, or carbamazepine for at least 7 days prior to study enrollment; patients receiving non-enzyme inducing anticonvulsants such as gabapentin or levetiracetam will be eligible
• Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma
• Patients with symptoms of congestive heart failure are not eligible
• Patients must not have >= grade 2 diarrhea
• Patients must not have uncontrolled infection
• Patients with a history of grade 4 allergic reactions to anti-GD2 antibodies or reactions that required discontinuation of the anti-GD2 therapy are not eligible
• Patients with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible

Where it is running

• Arkansas Children's Hospital — Little Rock, Arkansas, United States
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States
• Kaiser Permanente Downey Medical Center — Downey, California, United States
• Loma Linda University Medical Center — Loma Linda, California, United States
• Children's Hospital Los Angeles — Los Angeles, California, United States
• Valley Children's Hospital — Madera, California, United States
• Kaiser Permanente-Oakland — Oakland, California, United States
• Children's Hospital of Orange County — Orange, California, United States
• Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
• Sutter Medical Center Sacramento — Sacramento, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• Rady Children's Hospital - San Diego — San Diego, California, United States
• UCSF Medical Center-Parnassus — San Francisco, California, United States
• UCSF Medical Center-Mission Bay — San Francisco, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center — Denver, Colorado, United States
• Connecticut Children's Medical Center — Hartford, Connecticut, United States
• Yale University — New Haven, Connecticut, United States
• Alfred I duPont Hospital for Children — Wilmington, Delaware, United States
• MedStar Georgetown University Hospital — Washington D.C., District of Columbia, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Lee Memorial Health System — Fort Myers, Florida, United States
• Golisano Children's Hospital of Southwest Florida — Fort Myers, Florida, United States
• University of Florida Health Science Center - Gainesville — Gainesville, Florida, United States
• Phoenix Childrens Hospital — Phoenix, Arizona, United States

Full record on ClinicalTrials.gov

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