To improve survival and qualitity of life in patients with LAPC using ablative treatment with MRgRT (5x10Gy) in addition to standard of care.
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is health-related quality of life deterioration-free
survival, defined as the Time Until Definitive
Deterioration (TUDD) including death from any cause, calculated from the time
of randomization.
HRQoL is primarily assessed using the EORTC QLQ-C30 (version 3.0) Summary
Score. TUDD is defined as a definitive deterioration of >=10 points on Summary
Score (with no further improvement of >=10 points afterwards) or death from any
cause are considered an event. HRQoL is assessed longitudinally at inclusion
(baseline, prior to MRgRT), after two weeks, after four weeks and every
subsequent two months until end of study follow-up or death.
Secondary outcome
Secondary objectives in both study arms are:
- To assess individual components of the composite endpoint (HRQoL Summary
Score, overall survival)
- To assess other HRQoL components from the EORTC QLQ-C30 and HRQoL according
to the EORTC QLQ-PAN26 and EQ5D-5L questionnaires23-25
- To assess continuation of systemic therapy and/or administration of
subsequent treatments (e.g., surgery, second-line systemic treatment,
experimental treatment in clinical studies etc.), recommendations from
multidisciplinary team meetings, reasons for refraining from recommended
therapy, and reasons for discontinuation of therapy (i.e., start of best
supportive care)
- To assess tumor response on imaging according to RECIST criteria in patients
who receive imaging procedures during follow-up (no part of the trial
follow-up)26
- To assess the need for palliative interventions (pain medication, stent
placement, bypass surgery)
- To assess the cost-effectiveness (early Health Technology Assessment)
- To assess serum CA 19-9 response in patients in whom serum CA 19-9 is
measured (no part of the trial follow-up)
- To assess the feasibility of Trial@home monitoring devices for home
monitoring of pancreatic cancer patients
- To quantify the correlation of the obtained digital data from Trial@home with
clinical endpoints
- To exploratively generate new digital biomarkers from the data collected from
Trial@home (e.g., early signs of adverse evernts, clinical deterioration and/or
quality of life)
Secondary Objectives for the intervention arm only are:
• To assess acute (3 months) RT-related toxicity measured from the start of
MRgRT, according to CTCAE v527
• To assess completion of therapy
• To assess correlation of diffusion weighted images at each treatment fraction
and the possible correlation with outcomes for patients treated on a 1.5T
MR-Linac
Exploratory endpoints in both study arms:
- To analyse tumor biopsies (fine-needle biopsies; FNB), tumor cytology
(fine-needle aspiration; FNA) and blood samples acquired in the diagnostic
work-up and follow-up, to identify subtypes that predict treatment response and
understand genetic, epigenetic, metabolic, and immune subtypes.
- To analyse medical imaging data acquired in the diagnostic work-up and
follow-up of patients to identify potential radiomics patterns / biomarkers,
and learn about the morphological changes in response to MRgRT and how those
related to response.
Background summary
About 40% of pancreatic cancer patients are diagnosed with locally advanced
pancreatic cancer (LAPC). Recommended treatment consists of chemotherapy to
prevent disease dissemination and prolong survival. Nevertheless, local tumor
growth causes severe morbidity, including pain, gastrointestinal obstruction
and malnutrition. This has a substantial negative impact on health-related
quality of life (HRQoL). Eventually, one-third of patients die due to local
tumor growth rather than from systemic disease spread. For palliation of
symptoms and improved local tumor control, potentially prolonging survival,
minimally-invasive ablative therapies are needed.
Online adaptive stereotactic Magnetic Resonance-guided radiotherapy (MRgRT) is
an innovative treatment modality that enables high-precision ablative therapy
for pancreatic tumors. This potentially improves radiotherapy efficacy without
increasing the risk of treatment-related toxicity. Consequently, MRgRT holds
promise for treatment of pancreatic cancer.
Study objective
To improve survival and qualitity of life in patients with LAPC using ablative
treatment with MRgRT (5x10Gy) in addition to standard of care.
Study design
LAPSTAR is a multicenter randomized trail. (RCT).
All patients in the Netherlands with LAPC who cannot undergo surgery after
initial systemic therapy with (m)FOLFIRINOX or gemcitabine/nab-paclitaxel can
be included.
Randomization will take place after obtaining informed concentrations. Patients
will be randomized 1:1 into the intervention or control arm.
Patients in the intervention arm will be treated with 5x10Gy MRgRT in
combination with standard treatment. MRgRT will be performed at one of the
consortium centers (UMCU, AUMC, Radboudumc or Catharina Hospital).
Standard treatment may include chemotherapy ((m)FOLFIRINOX or
gemcitabine/nab-paclitaxel) or other supportive therapies.
Patients in the control arm will receive the standard treatment and will not
receive additional therapy.
During the study, patients will be asked to complete quality of life
questionnaires (EORTC QLQ-C30, EORTC QLQ-PAN26, EQ5D-5L)).
Follow-up time is 18 months.
Intervention
Ablative MR-guided radiotherapy (MRgRT) in addition to standard of care,
consitsting of 5x10 Gy MRgRT.
Study burden and risks
Patients in the interventional arm have minimal additional risks compared to
patients in the control arm. There is a very small risk of harm due to MRgRT.
The most common side effects of radiation therapy are: fatigue, pain,
diarrhoea, nausea, weight loss and intestinal discomfort. These
side effects, however, often improve quickly in the period after radiotherapy.
Serious side effects such as obstruction
perforation and bleeding of the gastrointestinal tract are rare.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
- Pathology proven pancreatic ductal adenocarcinoma (PDAC);
- At least two (preferably four) months systemic therapy with (m)FOLFIRINOX
and/or gemcitabine + nab-paclitaxel; or eligibility for chemotherapy but no
initiation of chemotherapy based on patients* wish;
- No option for surgical resection, either because anatomical irresectability
based on the surgeon*s judgement (assessed on imaging or during explorative
laparotomy) and/or frailty (unfit for surgery or chemotherapy) and/or no
surgery based on patient's wish.
- No evidence of distant metastatic disease progression, evaluated by CT Thorax
/ Abdomen / Pelvis and/or PET-CT scan;
- Performance status WHO 0-2.
Exclusion criteria
- Contra-indications for MRI or CT with an intravenous contrast agent according
to the protocol of the local radiology and/or radiotherapy departments
- Contraindications for MRgRT, as determined by the involved expert radiation
oncologists of the Consortium
- <18 years old
- Pregnancy
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
No registrations found.
In other registers
Register | ID |
---|---|
ClinicalTrials.gov | NCT06272162 |
CCMO | NL85622.041.24 |