recurrent or progressive high-risk Neuroblastoma MedDRA version: 21.0 Level: PT Classification code 10066595 Term: Neuroblastoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Celecoxib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: CELECOXIB
Other descriptive name: CELECOXIB
Trade Name: LASTET® 25 mg Weichkapseln
Product Name: Etoposid
Pharmaceutica
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
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 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
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 o Peripheral neuropathy or constipation CTCAE grade 3 or 4 o Cardiac arrhythmias (sinus bradycardia for age, sinus arrhythmia as 2.-3. grade AV block) o Pre-existing recurrent symptomatic bronchial asthma o Clinically manifest Diabetes mellitus (propranolol covers symptoms of hypoglycemia) o Conditions with low blood pressure below age-dependent normal ranges o History of gastrointestinal ulcer or perforation o Known 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary trial objective is to demonstrate the non-inferiority of event free survival (EFS) in children and adolescents = 2 and < 21 years of age with recurrent or progressive high risk neuroblastoma treated with low toxic metronomic celecoxib therapy in combination with low-dose metronomic cyclophosphamide, etoposide and vinblastine in comparison to a historical control group. Event free survival (EFS) defined as time from start of treatment up to: Progression (emerged from residual tumor, PD) or recurrence (developing from CR achieved by metronomic treatment), drop-out for unacceptable toxicity, secondary malignant neoplasm or death of any reason;Secondary Objective: •Disease control rate at 6 and 12 months of metronomic treatment defined as overall CR, PR or SD. •Response rate at 6 and 12 months (CR or PR) •Overall survival (OS) •Quality of life •Number of days of hospitalization during treatment time •Number of days with transfusion of blood products during treatment period •Duration of response (CR or PR) •Best overall response •Drop-out rate due to patients’ wish during metronomic treatment for another therapy •Surrogate biomarker analysis for angiogenesis and immunological function in blood •Safety and toxicity (adverse event profile) of metronomic therapy ;Primary end point(s): Event free survival (EFS) defined as time from start of treatment up to: Progression (emerged from residual tumor, PD) or recurrence (developing from CR achieved by metronomic treatment), drop-out for unacceptable toxicity, secondary malignant neoplasm or death of any reason;Timepoint(s) of evaluation of this end point: This clinical trial ends once 17 events (as defined by the trial protocol) have been reached. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Disease control rate at 6 and 12 months of metronomic treatment defined as overall CR, PR or SD. •Response rate at 6 and 12 months (CR or PR) •Overall survival (OS) •Quality of life •Number of days of hospitalization during treatment time •Number of days with transfusion of blood products during treatment period •Duration of response (CR or PR) •Best overall response •Drop-out rate due to patients’ wish during metronomic treatment for another therapy •Surrogate biomarker analysis for angiogenesis and immunological function in blood •Safety and toxicity (adverse event profile) of metronomic therapy ;Timepoint(s) of evaluation of this end point: either at the end of trial treatment of the patient or at the end of the trial (once 17 events have been reached) | — |
Countries
Germany
Contacts
Public ContactNeuroblastomstudie
Children’s Hospital, University of Cologne
Outcome results
None listed