A clinical study to determine the efficacy and feasibility of the combination of propranolol, celecoxib and low dose metronomic application of oral cyclophosphamide, oral etoposide and i.v. vinblastine in children and adolescents with recurrent or progressive neuroblastoma without other treatment options

Phase 1

• Conditions: recurrent or progressive high-risk Neuroblastoma; MedDRA version: 21.0Level: PTClassification code 10066595Term: Neuroblastoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-004593-29-DE
• Lead Sponsor: niversity of Cologne

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-10-09
• Study Completion: 2023-06-29
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

•Newly diagnosed recurrent or progressive high risk neuroblastoma which progressed despite previous treatment (irrespective of the number of previous relapses/progressions).
•Age: = 2 years and < 21 years
•diagnosis of neuroblastoma confirmed according to INSS criteria (Brodeur 1993)
- histological diagnosis from tumor tissue or
- presence of distinct neuroblastoma cells in the bone marrow and elevated catecholamine metabolites (VMA, HVA) in blood or urine
•High risk neuroblastoma as defined by
- INSS stage 4 (INRG stage M) neuroblastoma, > 1 year at initial diagnosis, or
- MYCN amplified neuroblastoma of any stage
•Recurrence (from CR) or progression (from PR or SD) is defined by detection of new lesions or >25% increase of pre-existing residual neuroblastoma (according to INSS criteria).
•Presence of measurable or evaluable disease
•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 (Lansky/Karnowski performance scale = 60)
•No serious active infection
•Spontaneous recovering blood counts
•Physical and psychosocial ability to comply with scheduled follow-up and with management of toxicity
•Females of childbearing age must have a negative urine pregnancy test prior to starting the study drug
•Written informed consent of parents or legal guardian and / or patient if applicable according to age and status of psycho-intellectual development
Are the trial subjects under 18? yes
Number of subjects for this age range: 26
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 26
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 (see 4.7.6.1) 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 or metabolites of the trial medication
•Severe medical or psychosocial conditions preventing trial participation and/or any of the following
oPeripheral neuropathy or constipation CTCAE grade 3 or 4
oCardiac arrhythmias (sinus bradycardia for age, sinus arrhythmia as 2.-3. grade AV block)
oPre-existing recurrent symptomatic bronchial asthma
oClinically manifest Diabetes mellitus (propranolol covers symptoms of hypoglycemia)
oConditions with low blood pressure below age-dependent normal ranges
oHistory of gastrointestinal ulcer or perforation
oKnown active HBV, HCV or HIV infection
•Concomitant participation in other clinical trials with investigational drugs or competing interventions including competing medications
•Pregnant women (Females of childbearing age must have a negative urine pregnancy test prior to starting the study drug)
•Female patients who are lactating not willing to stop breast-feeding
•Sexually active patients who are not willing to use/ not using a highly effective contraception method

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified