The goal of this study is to determine whether radiosensitization with carboplatin or the addition of Isotretinoin to maintenance therapy improves cure rates for children with other than average risk medulloblastoma/PNET.
ID
Source
Brief title
Condition
- Nervous system neoplasms malignant and unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine whether carboplatin radiosensitization increases long term
event-free survival for high risk
medulloblastoma/PNET patients.
To determine whether Isotretinoin increases long term event-free survival for
high risk
medulloblastoma/PNET patients.
Secondary outcome
To compare residual disease response to radiation alone versus radiation plus
carboplatin.
To identify molecular prognostic indicators suitable for patient stratification
in future trials.
Background summary
Medulloblastoma is the most common malignant childhood brain cancer. Standard
treatment for children with other than average risk medulloblastoma consists of
surgery, followed by radiation therapy and chemotherapy. The goal of this study
is
to determine whether radiosensitization with the addition of carboplatin during
radiation therapy improves the poor cure rates (50-60%) for children with
other than average risk medulloblastoma.
Carboplatin has activity as a single agent against medulloblastoma and it has
been shown to enhance radiation-induced tumor cell kill. A previous study,
CCG-99701, demonstrated that it was feasible and safe to administer carboplatin
on a daily basis during radiation
therapy.
Patients will be randomly assigned to receive carboplatin radiosensitization or
not. Primary outcome measurement will be eventfree survival.
This protocol previously included a randomization to 4 study arms, two of which
(arm C and C with the addition of Isotretinoin in maintenance treatment) have
been closed now (amendment 3). Arm A and B remain open to answer the question
whether the addition of carboplatin during radiotherapy will lead to a beter
event free survival,
This protocol also previously included supratentorial primative neuroectodermal
tumor (PNET) patients in addition to medulloblastoma patients. The PNET
component of the trial has concluded due to new insights regarding molecular
biology. This tumor is so much different from medulloblastoma that
heterogeneity of tretment effects across tumor types may recude power. The
study has been re-powered allowing additional inclusion of 100 patients
(amendment 2).
Study objective
The goal of this study is to determine whether radiosensitization with
carboplatin or the addition of Isotretinoin to maintenance therapy improves
cure rates for children with other than average risk medulloblastoma/PNET.
Study design
This is a mulitcenter phase III randomized factorial-designed open study. All
patients will be randomised to receive radiation therapy with or without
carboplatine and chemotherapy with or without the addition of isotretionoine
during the maintenance fase. The study arms with isotretinoine have already
been closed as per 01/27/2015 (amendment 3).
Intervention
Treatment comparisons will be made between induction radiation therapy alone to
radiation therapy and carboplatin, both followed with maintenance therapy with
or without isotretinoin.
Study burden and risks
The risks that are associated with this study involve the potential side
effects of the administration of carboplatin during radiotherapy.
The risks that were associated with the addition of isotretinoin to
consolidation/maintenance therapy are not applicable anymore, i.e. after the
second randomisation being closed.
Also the extra burden for study participants involving a longer treatment
duration (24 weeks longer) for patients treated with isotretinoine during
maintenance phase, does no longer apply.
The risks and burden involved with this treatment are justified by (1) the
overall goal to improve event free survival of high-risk medulloblastoma; (2)
the proved safety of the drug doses used in this trial; and (3) adequate
monitoring of study subjects during and after treatment
Zinkwerf 5-7
Den Haag 2545 CCE
NL
Zinkwerf 5-7
Den Haag 2545 CCE
NL
Listed location countries
Age
Inclusion criteria
Age greater or equal to 3 y and less than 22 y at time of diagnosis
Newly diagnosed previously untreated medulloblastoma (M0 with >1.5 cm2 residual, or M1-3); (amendment 2: inclusion sPNET discontinued)
Written informed consent (parents and patient)
Exclusion criteria
Age less than 3 y
Extraneural metastases
Karnofski/Lansky < 50% and life expectancy <= 8 weeks
Inadequate organ function prior to start of therapy (renal, liver, bonemarrow)
Previous chemotherapy or radiation therapy
Other experimental therapy
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-016059-23-NL |
| ClinicalTrials.gov | NCT00392327 |
| CCMO | NL29915.091.09 |
| OMON | NL-OMON21835 |