To determine the prevalence of actionable genetic alterations in PDAC patients
ID
Source
Brief title
Condition
- Exocrine pancreas conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main endpoint is determining the percentage of patients with clinically
actionable genetic alterations. These alterations are defined as (1) a
pathogenic variant that is target of an approved drug in any cancer indication
or predicts sensitivity to an approved drug in any cancer indication (e.g. MSI
and pembrolizumab), (2) a pathogenic variant that is in the same pathway as a
variant that is the target of an approved drug in any cancer indication or (3)
a pathogenic variant that has compelling clinical or biological evidence
supporting being predictive of response to a drug in PDAC. Clinically
actionable mutations are selected using the OncoKB database52 and scientific
literature.
Secondary outcome
Feasibility
Feasibility is a composite endpoint of:
• The number of included patients within a one year period. Which is deemed
feasible if 200 patients are included within a one-year period.
• The percentage of patients successfully undergoing NGS. Which is deemed
feasible if the NGS is successful in 80% of the submitted samples. Including a
subgroup analysis of treatment naïve tissue versus tissue after
chemo(radio)therapy.
• Results reported back to the local clinician within relevant time-frame. The
relevant time-frame is defined as the molecular tumor profiling report
available within 4 weeks after acquisition of tissue and advice of the
molecular tumor board within 8 weeks after the acquisition of tissue.
Changes in clinical management
Percentage of patients potentially experiencing a change in clinical management
as result of the NGS. This is a change in treatment or referral to the clinical
geneticist as a result of the NGS.
Subgroup identification
For the identification of subgroups with more clinically actionable mutations,
the incidence will be compared between pre-specified subgroups based on
baseline variables, including; age (age < 50 years vs. age 50-60 years),
gender, smoking status, disease status (primary, metastatic), tumor biopsy
site, metastatic sites, treatment status (treatment naïve, neoadjuvant
chemo(radio)therapy), oncologic history and familial history.
Survival outcomes and therapy outcomes
Therapy outcomes and survival data will be obtained from electronic patient
records from routine hospital visits, up to 5 years after primary diagnosis.
The following endpoints are included:
• Overall survival, defined as the time interval between the day of primary
diagnosis and the date of the occurrence of death (all causes).
• Cancer-specific survival, defined as the time interval between the day of
primary diagnosis and the date of the occurrence of death caused by PDAC.
• Disease-free survival, defined as the length of time between the day of
resection with curative intent and the date of local recurrence, regional
recurrence, occurrence of distant metastases or death (all causes), whichever
occurs first. Date of recurrence or metastasis occurrence is determined by
first suspicion on CT scan.
• Local recurrence-free survival, defined as the length of time between the day
of resection with curative intent and the date of local recurrence, regional
recurrence or death (all causes), whichever occurs first. Date of recurrence is
determined by first suspicion by CT.
• Distant metastasis-free survival, defined as the length of time between the
day of resection with curative intent and the date of the occurrence of distant
metastases or death (all causes), whichever occurs first. Date of occurrence of
metastasis is determined by first suspicion by CT.
• Progression-free survival, defined as the length of time between start of
systemic treatment and the date of progression of disease or death (all
causes), whichever occurs first. Date of progression is determined by first
suspicion on CT scan.
Therapy outcomes included response to (systemic) therapy according to
RECIST-criteria and treatment toxicity according to CTCAE version 5.0.
Concordance rate
The concordance rate for individual genes and the overall concordance rate (all
genes in the ctDNA panel) in ctDNA alterations compared to tumor tissue NGS DNA
alterations.
Background summary
Pancreatic cancer is an aggressive disease that is difficult to treat. Some of
the patients undergo surgery to remove the tumor. Unfortunately, in many
patients, the pancreatic cancer comes back after it has been removed. The
treatment for advanced pancreatic cancer is usually chemotherapy. If the cancer
no longer responds to chemotherapy, there are few other treatment options. So
there is a need for new and better treatment methods.
Pancreatic cancer is caused by genetic abnormalities in the tissue of the
pancreas. Some of these abnormalities can be treated with targeted drugs. Most
patients with pancreatic cancer have genetic abnormalities for which
unfortunately there is no effective medicine (yet). In this study we try to get
a better picture of which genetic abnormalities are present in the tumors of
relatively young pancreatic cancer patients. We are particularly interested in
genetic abnormalities that could possibly be treated with targeted drugs. These
treatments are currently usually only given within a study context to patients
who no longer respond to chemotherapy.
Study objective
To determine the prevalence of actionable genetic alterations in PDAC patients
<= 60 years old.
Study design
Translational, multicenter cohort study.
Study burden and risks
For NGS, formalin-fixed paraffin embedded (FFPE) tissue is required to yield a
sufficient percentage of tumor content (RNA analysis = 10%, DNA analysis =
20%). The tissue of patients that undergo resection of their tumor or a core
biopsy during regular diagnostic work-up can be used for next generation
sequencing (NGS). In patients who present with disease recurrence after
resection archived FFPE tissue of the resected primary tumor can be used. In
case of metastatic PDAC patients with insufficient or no histological tissue
available for NGS an additional core biopsy is required. These patients will be
offered a core biopsy of the metastasis, which is considered a safe procedure.
At the moment of inclusion the majority of the PDAC patients will have
metastatic disease. For these patients there are limited therapeutic options
which are mainly based on systemic chemotherapy, offering a median overall
survival of 8.5-11 months. In the subgroup of patients identified with an
actionable genetic alteration, enrolment in a subsequent basket trial for
targeted therapy might offer improved survival. Considering this, the potential
benefit of participation in this study outweighs the above mentioned burden and
risks.
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
• Cytological or histologically confirmed PDAC, irrespective of treatment
status;
• Age > 18 years and <= 60 years at date of primary diagnosis;
• Performance status of ECOG 0-2;
• Estimated life expectancy of at least 12 weeks;
• Written informed consent.
Exclusion criteria
• Unwilling to know if there are any alterations which might be associated with
genetic predisposition of cancer;
• Patient with locally-advanced PDAC or local-recurrence of PDAC with no
histological tissue available for NGS.
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 |
|---|---|
| CCMO | NL75415.078.20 |