Sorafenib and Cyclophosphamide/Topotecan in Patients With Relapsed and Refractory Neuroblastoma

Running, not enrolling · Phase 1

Conditions studied: Neuroblastoma

In brief

This study will combine three drugs: sorafenib, cyclophosphamide and topotecan. Adding sorafenib to cyclophosphamide and topotecan may increase the effectiveness of this combination. The investigators first need to find out the highest dose of sorafenib that can be given safely together with cyclophosphamide and topotecan. This is the first study to test giving these three drugs together and will help determine the highest dose of sorafenib that can safely be given together with cyclophosphamide and topotecan to patients with resistant/relapsed neuroblastoma.

Key facts

Study ID

NCT02298348

Run by

New Approaches to Neuroblastoma Therapy Consortium

People needed

18

Starts

2015-10-08

Expected to finish

2026-12-01

Last updated by the study team

2026-03-23

Who can join

Age: any, up to 30. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must be < 30 years of age when registered on study.
• Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
• Patients must have high-risk neuroblastoma according to COG risk classification at the time of study enrollment. Patients who were initially considered low or intermediate risk, but then reclassified as high risk are also eligible.
• Patients must have at least ONE of the following:
• Recurrent/progressive disease at any time prior to study enrollment - regardless of response to frontline therapy.
• Refractory disease: persistent sites of disease after achieving a best overall response of no response to front line therapy after a minimum of 4 cycles of induction therapy AND patient has never had recurrent/progressive disease.
• Persistent disease: persistent sites of disease after achieving a best overall response of partial response to frontline therapy after a minimum of 4 cycles of induction therapy AND patient has never had recurrent/progressive disease.
• Patients must have at least ONE of the following (lesions may have received prior radiation therapy as long as they meet the other criteria listed below):
• At least one MIBG avid bone site or diffuse MIBG uptake.
• For recurrent/progressive or refractory disease, a biopsy is not required regardless of number of MIBG avid lesions
• For persistent disease, if patient has only 1 or 2 MIBG avid lesions OR a Curie core of 1 - 2, then biopsy confirmation of neuroblastoma and/or ganglioneuroma in at least one site present at the time of enrollment (bone marrow, bone or soft tissue) is required to be obtained at any time point prior to enrollment and two weeks subsequent to most recent prior therapy. If a patient has 3 or more MIBG avid lesions OR a Curie Score of ≥ 3 then no biopsy is required for eligibility.
• Any amount of neuroblastoma tumor cells in the bone marrow based on routine morphology (with or without immunocytochemistry) in at least one sample from bilateral aspirates and biopsies.
• At least one soft tissue site that meets criteria for a TARGET lesion defined by:
• Size: Lesion can be accurately measured in at least one dimension with a longest diameter ≥ 10mm, or for lymph nodes ≥ 15mm short axis. Lesions meeting size criteria will be considered measurable.
• In addition to size, a site needs to meet one of the following criteria:
• MIBG avid. For patients with persistent disease only: If a patient has only 1 or 2 MIBG avid lesions OR a Curie Score of 1 - 2, then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one site present at time of enrollment (either bone marrow, bone and/or soft tissue) is required to be obtained at any time point prior to enrollment and at least two weeks subsequent to most recent prior therapy. If a patient has 3 or more MIBG avid lesions OR a Curie Score of ≥ 3 then no biopsy is required for eligibility.
• FDG-PET avid (only if tumor known to be MIBG non-avid). These patients must have had a biopsy confirming neuroblastoma and/or ganglioneuroblastoma in at least one FDG-PET avid site present at the time of enrollment done prior to enrollment and at least two weeks subsequent to the most recent prior therapy.
• Non-avid lesion (both MIBG and FDG-PET non-avid). These patients must have had a biopsy confirming neuroblastoma and/or ganglioneuroblastoma in at least one non-avid lesion present at the time of enrollment done prior to enrollment and at least two weeks subsequent to the most recent prior therapy.
• Patients must have a life expectancy of at least 8 weeks and a Lansky (< 16 years age) or Karnofsky (> 16 years age) score of at least 50
• Patients must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy prior to study enrollment.
• Patients must not have received the therapies indicated below for the specified time period prior to the first day of administration of protocol therapy on this study:
• Myelosuppressive chemotherapy: Last dose was given at least 14 days before the start date for protocol therapy.
• Biologic (anti-neoplastic agent including retinoids): Last dose given at least 7 days prior to the start date for protocol therapy.
• Monoclonal antibodies: Last dose of any monoclonal antibodies must have received at least 7 days or 3 half-lives, whichever is longer, prior to the start date for protocol therapy. Please refer to table posted at www.nant.org for definition of half-lives for specific monoclonal antibodies.
• Patients must not have received radiation for a minimum of two weeks prior to study enrollment.

You may not qualify if…

• Subjects with calculated BSA < 0.40 m2 are not eligible for study participation as Sorafenib dosing for this study cannot accommodate subjects of this size utilizing commercially available drug formulation.
• Pregnancy: Serum B-HCG must be negative in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events.
• Patients who have an active or uncontrolled infection are excluded. Patients on prolonged antifungal therapy are still eligible if they are culture and biopsy negative in suspected radiographic lesions and meet other organ function criteria.
• Patients with prior allogeneic transplant are not eligible.Patients with a documented history of cerebrovascular accidents and/or TIA within the past 6 months are not eligible.
• Patients with a history of intracranial hemorrhage are not eligible.
• Patients with a history of venous or arterial thrombosis personally or in a first degree relative before the age of 40 years are not eligible unless the thrombotic event was associated with a central line.
• Patient with prolonged QT/QTc (defined as QTc interval > 450 msec) are not eligible.
• Patient declines participation in NANT 04-05. (Neuroblastoma Biology Study)

Where it is running

• Children's Hospital Los Angeles — Los Angeles, California, United States
• UCSF Comprehensive Cancer Center — San Francisco, California, United States
• Children Hospital of Colorado — Aurora, Colorado, United States
• Children's Healthcare of Atlanta — Atlanta, Georgia, United States
• University of Chicago, Comer Children's Hospital — Chicago, Illinois, United States
• Childrens Hospital Boston, Dana-Farber Cancer Institute. — Boston, Massachusetts, United States
• C.S Mott Children's Hospital — Ann Arbor, Michigan, United States
• University of North Carolina — Chapel Hill, North Carolina, United States
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
• Cook Children's Healthcare System — Fort Worth, Texas, United States
• Children's Hospital and Regional Medical Center - Seattle — Seattle, Washington, United States
• Hospital for Sick Children — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

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