To analyse the number of patients with (germline/somatic) actionable molecular aberrations in patients with relapsed/refractory pediatric tumors for whom no standard treatment or study protocol is available.
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
-The number of all included patients in which an actionable lesion could be
identified divided by the number of all included patients
Secondary outcome
-The total number of pediatric oncology patients in the Netherlands each year
with relapsed/refractory malignant disease for whom no standard protocol or
treatment is available (per protocol population)
-The number of patients who are able to undergo a diagnostic tumor biopsy (as
standard of care) divided by all included patients (protocol population)
-The number of patients with tumor biopsies associated/procedure-related
complications divided by all patients that underwent a tumor biopsy
-The number of patients in which tumor material was obtained of sufficient
quality for molecular profiling divided by the total number of patients that
underwent a biopsy
-The number of patients in whom actionable lesions were identified divided by
the number of patients in who a molecular profile was obtained.
-The number of patients with a germline mutation in a cancer predisposition
gene divided by the number of patients in whom germline mutational screening
was successful.
-The number of patients for whom organoid culture is successful divided by the
number of patients for whom residual living cells were available for organoid
culture.
-The number of patients for whom results from the compound screening are
available divided by the number of patients for whom organoid culture was
successful.
-The number of patients in which the molecular tumor board is able to provide a
treatment advice to the treating physician divided by all patients in whom
actionable lesions were identified
-The time frame between the date of the biopsy and the date of the treatment
advice by the molecular tumor board
-The number of patients treated according to the treatment recommendation
divided by the total number of patients in which the molecular tumor board
provided a treatment advice
-Major side-effects observed in the patients treated will be described.
-Treatment response in solid tumors (complete response, partial response,
stable disease or progression) will be assesses using the RECIST criteria.26 In
leukemia, complete remission is defined as less than 5% blast cells in the bone
marrow.
-Survival parameters overall survival (the percentage of people who are still
alive one year after inclusion in the study) and progression-free survival (the
time between inclusion in the study until the time that the disease progresses
or the patient dies from any cause). Both OS en PFS will be estimated in the
entire cohort of patients using the Kaplan-Meier estimator.
Background summary
Significant progress has been made in the cure of pediatric cancer through
treatment optimization (chemotherapy, radiotherapy and surgery) and improvement
of supportive care. Despite major advances, 25% of children with cancer
ultimately die due to lack of effective treatment. New treatment modalities are
urgently needed. The most promising option is the development of targeted
therapy in which a genetic aberration in the tumor is targeted by small
molecules. This however requires that the tumor biology is deciphered to
identify tumor-driving genetic aberrations.
Study objective
To analyse the number of patients with (germline/somatic) actionable molecular
aberrations in patients with relapsed/refractory pediatric tumors for whom no
standard treatment or study protocol is available.
Study design
This is a non-randomized single-arm observational study aimed at molecular
profiling of tumor biopsy samples and germline tissue, taken during a standard
of care biopsy procedure to confirm relapsed or refractory malignancy, from
patients with relapsed/refractory pediatric tumors.
Study burden and risks
The main aim of this study is to identify actionable lesions in cancers arising
in children to develop personalized medicine. Therefore minors have to be
included in the study. There are no risks associated with participation in this
study, as the biopsy will be performed as standard of care. The study consists
of molecular profiling of germ line and tumor material with the aim to identify
actionable lesions, which will be prioritized by a molecular tumor board. In
addition, patient characteristics and clinical follow-up will be collected. If
actionable lesions are identified and the patient is treated with a targeted
drug (by enrollment in a separate clinical trial, on compassionate use basis,
or off-label use of a commercial drug), the patient might benefit from the
diagnostics performed in this study. Treatment interventions are not part of
this study protocol but data will be captured as part of this registry. In case
germ line aberrations are detected and the patient and/or parents have declared
they want to be informed, the treating physician will be informed and the
patient/parents will be referred to a clinical geneticist for confirmation of
the detected germ line mutation and further counseling.
Heidelberglaan 25
Utrecht 3584 CS
NL
Heidelberglaan 25
Utrecht 3584 CS
NL
Listed location countries
Age
Inclusion criteria
Children and adolescents with pediatric tumors (<30 years of age) can be
enrolled into this study when a relapse or a refractory tumor is clinically
suspected for whom no standard treatment protocol is available and when
informed consent is obtained.
Exclusion criteria
when biopsy is considered unsafe or severe organ toxicity precludes undergoing
any of the procedures mentioned in the protocol. Also any other condition that
may hamper participation according to the treating physician.
Design
Recruitment
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 |
|---|---|
| Other | Nederlands Trial Register 5915 |
| CCMO | NL56826.078.16 |
| OMON | NL-OMON29251 |