Primary aimTo determine the prevalence of children with hearing loss at time of discontinuation of cancer therapy in a prospective full cohort of 600 children with solid and CNS tumors.The secondary objectives of this study are:- To study the…
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Source
Brief title
Condition
- Inner ear and VIIIth cranial nerve disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary study parameters:
The primary objective of this study is to determine the prevalence of children
with hearing loss at time of discontinuation of cancer therapy in a prospective
full cohort of 600 children with solid and CNS tumors.
The definition of hearing loss will be:
Pure tone audiometry: sensorineural hearing loss >40dB at >=4kHz, (corresponding
to Munster grade >=2B)
Frequency specific Auditory Brain Stem Response or Visual Reinforcement
Audiometry : a sensorineural hearing loss >40 dB at >= 4 kHz.
Secondary outcome
Secondary outcomes: tinnitus and vertigo.
Determinants: co-medication, cisplatin/ carboplatin dosage and levels, age,
sex, CNS-/ENT irradiation, ENT surgery, neurosurgery.
Liver and kidney function serum measurements are part of standard care during
childhood cancer treatment. The results of these standard care measurements
will be collected because platinol and co-medication are often excreted by
liver and/or kidneys.
Background summary
In The Netherlands, approximately 600 children are diagnosed with childhood
cancer annually. Childhood cancer survival rates reach up to about 75-80%
because of beter stratification and treatment. Ototoxicity, which includes
hearing loss, tinnitus and vertigo, is one of the direct and late sides effects
of cancer treatment. Over the past few years, it has become apparent that
platinum agents, CNS-/ENT (Ear-Nose-Throat) surgery and CNS-/ENT irradiation
are important risk factors for ototoxicity.
Irreversibel hearing loss occurs in up to 80% of childhood cancer survivors
that had received platinum agents. Tinnitus has been reported in up to 17% of
childhood cancer patients and survivors. At this moment large national
prospective cohorts of childhood cancer patients that were systematically
screened for ototoxicity have not been reported, this hampers estimation of
true frequencies and determinants like comedication such as antibiotics and
diurects which are often prescribed in oncology treatment protocols.
Determining prevalence and risk factors for ototoxicity will give insight in
which children will qualify for audiological screening in the future, and what
kind of interventions can be used to prevent ototoxicity.
Study objective
Primary aim
To determine the prevalence of children with hearing loss at time of
discontinuation of cancer therapy in a prospective full cohort of 600 children
with solid and CNS tumors.
The secondary objectives of this study are:
- To study the feasibility of standard of care audiological (hearing loss,
tinnitus and vertigo) testing of all patients with solid and CNS tumors treated
with platinum, CNS-/ENT irradiation, CNS-/ENT surgery, before and after
childhood cancer therapy by using standardized diagnostic tests, timing and
frequency of audiological evaluations in this population (stratum 1).
- To gain insight into the relative contribution of cancer treatment
components, clinical characteristics and supportive care co-treatment
(aminoglycosides, loop diuretics, and vancomycin) on hearing loss in children
with solid and CNS tumors that do receive platinum derivates and/or CNS-/ENT
irradiation and/or CNS-/ENT surgery by performing standard audiological testing
at the end of treatment (stratum 1).
- To gain insight into the relative contribution of supportive care medication
(aminoglycosides, loop diuretics, and vancomycin) on hearing loss in children
with solid and CNS tumors that do not receive platinum derivates and/or
CNS-/ENT irradiation and/ or CNS-/ENT surgery, by performing audiological
testing at the end of treatment (stratum 2).
- To determine the effect of platinum dose and levels, irradiation dose,
co-medication dose and levels on ototoxicity at the end of treatment (stratum
1).
- To gain insight in the frequency and characteristics of patients with
abnormalities in audiological testing (hearing loss, tinnitus and vertigo)
occurring during childhood solid tumor and CNS cancer treatment (stratum 1 and
2).
- To create a registry with outcomes of audiological evaluations and potential
determinants for ototoxicity during childhood cancer therapy (stratum 1 and 2),
which can be used for further research on innovation and enhancing of
audiological testing and genetic susceptibility studies.
Study design
A dedicated research nurse and research physician will identify, approach and
follow all newly diagnosed children with solid and CNS tumors. Stratified on
age, patients will get a standard audiological assessment at baseline (before
cancer therapy) and within 3 months after end of treatment as defined in the
SOUND protocol (stratum 1 and 2).
Tinnitus and vertigo screening:
In the current study, anamnestic screening for tinnitus and vertigo will
already be performed during audiological assessments before and shortly after
end of cancer treatment as a standardized procedure for all patients. Described
in the research protocol on pages 25-26
Platinum levels:
For inclusion of cisplatin and carboplatin pharmacokinetics in a subset of
patients in stratum 1, we will collaborate with the PIs of the PINOCCHIO-study
(coordinating investigators: Prof dr. C.M. Zwaan, Prof. dr. A.D.R. Huitema, and
dr. A. Lalmohamed; registration number NL63037.078.18; subsidized by the
Princess Máxima Center). This study started in February 2019 and aims to
determine pharmacokinetics of nine types of chemotherapy, including carboplatin
and cisplatin. Blood samples are being taken in the setting of the PINOCCHIO
study. Described in the research protocol on page 26.
Statistical analysis:
Baseline characteristics between patients with and without ototoxicity will be
assessed by applying X2-test (for categorical variables), Student*s t-test (for
normally distributed continuous variables), or Mann-Whitney test (for skewed
variables). A logistic regression model will be estimated to investigate the
effect of risk factors. To quantify the effect of prognostic factors on the
risk of ototoxicity at end of treatment, odds ratios along with 95% confidence
intervals will be estimated. Described in the research protocol on page 29.
Sampling design process:
In total, 600 patients will be included in 2 years, 400 patients in stratum 1
and 200 patients in stratum 2.
In patients of stratum 1, audiological assessments data are generated as
standard of care and will be collected in a registry after patients and/ or
parents have provided informed consent for standard of care data for scientific
research (biobank/ "over de drempel PIF"). In stratum 1 we expect that 10% of
patients can not be participate for obvious reasons and we estimate the
potential drop out during te study to be around 15%. 306 patients will be
available for final analysis in stratum 1.
In stratum 2 we expect that 10% will not participate and that 15% will drop out
during te study, 153 patients will be available for final analysis in stratum
2. As audiological assessments are not standard of care in stratum 2, an
interim analysis after inviting the first 100 patients will be performed. If <
5% of these patients has hearing loss (>= Muenster 2b), than we will not
included the last 100 patients. In that case 77 patients will be available for
final analysis. In stratum 2 audiological assessments are not part of standard
of care, therefore patients and/or parents will asked to sign a study specific
inform consent.
In two years, at least 383 patients (306 in stratum 1 and 77 in stratum in 2)
are available for final analysis. If we will find >= 5% hearing loss by interim
analysis in stratum 2, than 459 patients (306 in stratum 1 and 153 in stratum
2) will be available for final analysis. Sampling design process is described
in the research protocol on page 19 and 20.
Power-analysis.
We expect a frequency of 35% hearing loss at end of treatment (stratum 1 and
2). Univariate and multivariate analysis will be performed to investigate the
individual variables on the outcome of interest (hearing loss). Power analysis,
based on a 95% confidence interval for one proportions, showed that 367
patients are needed for these analysis. With at least 383 patients for final
analysis, we have enough power to performing univariate and multivariate
analysis. Power analysis is described on page 21 of the research protocol.
Study burden and risks
All patients will receive standard treatment according to current national and
international treatment-protocols. For patients in stratum 1, audiological
assessments are part of standard care, patients in stratum 2 will get an
audiological assessment twice. It takes two times 1 hour time extra to complete
these extra audiological assessments. An audiological assessment is free of
risk.
Heidelberglaan 25
Utrecht 3584 CS
NL
Heidelberglaan 25
Utrecht 3584 CS
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in stratum 1, a subject must meet all of
the following criteria:
1. Diagnosed with a CNS tumor or solid tumor in the Princess Máxima Center and
2. Planned to receive treatment with cisplatin and/or carboplatin and/ or
oxaliplatin and/or CNS-/ENT irradiation and/or CNS-/ENT surgery and will
receive audiological examination as part of standard of care;
3. Children aged 0 until 19 years at time of diagnosis;
4. Biobank/ "over de drempel PIF", Informed Consent Form (ICF) signed for
collection of standard of care data.
In order to be eligible to participate in stratum 2, a subject must meet all of
the following criteria:
1. Diagnosed with a CNS tumor or solid tumor in the Princess Máxima Center and
2. Not planned to receive treatment with cisplatin and/or carboplatin and/or
oxaliplatin, or planned to receive CNS-/ENT irradiation and/or CNS-/ENT surgery
without audiological examination as part of standard of care;
3. Children aged 0 until 19 at time of diagnosis;
4. Study specific informed consent form (ICF) signed prior to participation in
the study.
Exclusion criteria
1. Critically ill, Intensive Care unit admission.
2. Presence of a solid tumor/ CNS tumor not planned to receive chemotherapy
and/or planned to receive surgery or irradiation at other locations than the
CNS-/ENT area, or were a watch-and-wait approach is applicable;
3.Identification of a recurrence/relapse tumor
4.Infaust prognosis at time of diagnosis/ palliative treatment only
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL71985.041.20 |