Metronomic Treatment in Children and Adolescents With Recurrent or Progressive High Risk Neuroblastoma

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Neuroblastoma is the second most frequent cause for death from cancer in childhood. Already one year after diagnosis of recurrence from high risk neuroblastoma, 75% of the patients experience further progression.

Metronomic therapy is targeting not only the tumor cell, but also the tumor supplying vasculature and the interactions between Tumor and immune cells. The toxicity is expected to be low due to the low (but continuous) dosing of drugs.

The study investigates the tolerance and the efficacy of a new combination of five drugs consisting of propranolol (antiangiogenetic, anti-neuroblastic), Celecoxib (modulating immune response, ant-neuroblastic), cyclophosphamide (antiangiogenetic, anti-neuroblastic), etoposide (antiangiogenetic, anti-neuroblastic), and vinblastin (antiangiogenetic, anti-neuroblastic). Vinblastin is scheduled every 14 days intravenously, all other drugs are applied daily throughout 365 days (except etoposide for 4x3 weeks). The efficacies of each of the drugs have been demonstrated in vitro and in vivo in animal studies. All drugs have been used in children for other conditions. From those experiences low toxicities and a favorable Quality of life are expected.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Cologne
• Treatments: Celecoxib; Propranolol; Vinblastine

Criteria

Inclusion Criteria:

• Newly diagnosed recurrence or progression of high risk neuroblastoma which progressed despite previous treatment (irrespective of the number of previous relapses/progressions).

• Refractory and/or residual high-risk neuroblastoma with measurable or evaluable disease irrespective of preceding treatment (no Progression during the minimal interval as defined below)

• Age: ≥ 2 years and < 21 years

• Measurable or evaluable disease defined as

• Presence of at least one measurable (recurrent or newly progressing) neuroblastoma lesion ≥ 10 mm by magnetic resonance imaging (MRI) or computed tomography (CT) or

• Newly detected unambiguous scintigraphic (MIBG) avid bone and/or medullary lesions

• presence of unambiguous bone marrow metastasis

• Minimal interval between start of trial medication and preceding anti-cancer treatment is 4 weeks after chemotherapy, 6 weeks after radiotherapy, and 12 weeks after myeloablative therapy

• Life expectancy > 3 months

• Good to moderate general condition (performance scale ≥60)

• No serious infection

• Spontaneous recovering blood counts:

• White blood cell count ≥ 1000/µL

• Neutrophil count ≥ 500/µL

• Platelet count ≥ 25 000/µL (unsupported)

• Written informed consent of parents or legal guardian and/ or patient according to age and status of psycho-intellectual development.

Exclusion Criteria:

• Minimal residual disease status (only) without unambiguous measurable or evaluable disease

• Patients unable to swallow trial medication

• Any concomitant anti-cancer treatment (e.g. other cytostatic drugs, "small molecules", antibodies, radiotherapy, surgery of tumor or metastases)

• Treatment with medication that interact with study medication that cannot be discontinued at least one week prior to the start of trial medication and for the duration of the trial

• Intake of antihypertensive drugs, e.g. calcium channel blockers

• Established hypersensitivity to the active or one of the other constituents of the trial medication

• Severe medical or psychosocial conditions preventing trial participate and/or any of the following

• Peripheral neuropathy or constipation CTCAE grade 3 or 4

• Cardiac arrhythmias (sinus bradycardia for age, sinus arrhythmia as 2.-3. grade atrioventricular block)

• Pre-existing recurrent symptomatic bronchial asthma

• Diabetes mellitus (propranolol covers symptoms of hypoglycemia)

• Conditions with low blood pressure below age-dependent normal ranges

• History of gastrointestinal ulcer or perforation

• Known active hepatitis B virus (HBV), hepatitis C (HBC) virus or human immunodeficiency virus (HIV) infection

• Concomitant participation in other clinical trials with investigational drugs or with competing interventions

• Pregnancy, lactation

• Sexually active patients not willing to use highly effective contraception