A randomized controlled trial comparing the effect of local ablative MR-guided radiotherapy (MRgRT) after systemic therapy with current standard treatment alone, on health-related quality of life in patients with locally advanced pancreatic cancer (LAPC).
Rationale: About 40% of patients with pancreatic cancer are diagnosed with locally advanced pancreatic cancer (LAPC). Recommended treatment consists of chemotherapy to prevent disease dissemination and prolong survival. Nevertheless, local tumor growth often 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 may be effective. Online adaptive stereotactic Magnetic Resonance-guided radiotherapy (MRgRT) is an innovative treatment modality that enables high-precision ablative radiotherapy for pancreatic tumors. This potentially improves RT efficacy without increasing the risk of RT-related toxicity. Consequently, MRgRT holds promise for the treatment of pancreatic cancer. Objective: To investigate the efficacy of stereotactic MRgRT on HRQoL deterioration-free survival, including death as an event, in patients with LAPC after systemic chemotherapy. Study design: Nationwide randomized controlled trial (1:1 randomization). Study population: Patients with LAPC according to Dutch Pancreatic Cancer Group (DPCG) criteria who are not eligible for tumor resection after at least two months of chemotherapy (sample size 150 patients). Also, patients with LAPC who are eligible but choose to refrain from chemotherapy and/or surgery can participate in this trial. Intervention: Patients in the intervention arm receive 50Gy MRgRT in five fractions over two weeks in one of the four Consortium Centers, followed by standard care, either consisting of continuation of chemotherapy or best supportive care. Patients in the control arm continue standard care without ablative MRgRT. Main study endpoints: The primary outcome is HRQoL deterioration-free survival from the time of randomization, defined as the Time Until Definitive Deterioration (TUDD) including death as an event. HRQoL is evaluated using the EORTC QLQ-C30 Summary Score. The TUDD is defined as a 10-point minimal clinically important difference compared to baseline, with no further improvement of ≥10 points afterwards. All patients will be offered home monitoring using the Trial@home platform to decrease the burden of trial participation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
150
5 fractions of 10 Gray MRgRT in addition to standard of care
Catharina Hospital
Eindhoven, North Brabant, Netherlands
Amsterdam University Medical Center, VUmc
Amsterdam, North Holland, Netherlands
Radboud University Medical Center
Nijmegen, Netherlands
University Medical Center Utrecht
Utrecht, Netherlands
HRQoL deterioration-free survival
HRQoL deterioration-free survival is 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.
Time frame: Through study completion, an average of 18 months
Overall survival
The time interval between LAPC diagnosis and either death from any cause or last follow-up
Time frame: From the date of LAPC diagnosis untill either death from any cause or last follow-up, whichever came first, assessed up to 18 months
Patient reported Quality of Life EORTC QLQ-PAN26
Part of the Patient Reported Outcome Measures (PROMs) using EORTC QLQ-PAN26
Time frame: At baseline and at 2,4, weeks and subsequently every 2 months. Assessed through study completion, up to 18 months
Patient reported Quality of Life EORTC QLQ-C30
Part of the Patient Reported Outcome Measures (PROMs) using EORTC QLQ-C30
Time frame: At baseline and at 2,4, weeks and subsequently every 2 months. Assessed through study completion, up to 18 months
Patient reported Quality of Life EQ5D-5L
Part of the Patient Reported Outcome Measures (PROMs) using EQ5D-5L
Time frame: At baseline and at 2,4, weeks and subsequently every 2 months. Assessed through study completion, up to 18 months
The need of subsequent treatments
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)
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Time frame: Through study completion, an average of 18 months
Treatment response assessed on CT-imaging (graded according to RECIST guidelines)
To assess tumor response on imaging according to RECIST criteria in patients who received imaging procedures during follow-up (no part of the trial follow-up)
Time frame: with available imaging during 18 months follow-up
CA 19.9 response
To assess serum CA 19-9 response in patients in whom serum CA 19-9 is measured (no part of the trial follow-up)
Time frame: Through study completion, an average of 18 months
Trial@home monitoring related outcome: feasibility Withings Steel HR smartwatch
To assess the feasibility of the Trial@home monitoring via the Withings Steel HR smartwatch for home monitoring of pancreatic cancer patients. Compliance Withings Steel HR smartwatch (wear-time): amount of time (hours) in a day that the participant wears the smartwatch. This is calculated by the amount of time the device registers a heart rate. Patients wearing the device for \>50% of the observation period will be considered as feasible.
Time frame: Through study completion, an average of 18 months
Trial@home monitoring related outcome: feasibility Body+ scale
To assess the feasibility of the Trial@home monitoring via the Body+ scale for home monitoring of pancreatic cancer patients. Compliance rates Body+ scale: compliance with weekly weight measurements is calculated by the number of completed weight measurements divided by the total amount of weeks in the observation period. A compliance rate of at least 75% will be considered as feasible.
Time frame: Through study completion, an average of 18 months
Trial@home monitoring related outcome: feasibility Whitings Sleep
To assess the feasibility of the Trial@home monitoring via the Whitings Sleep for home monitoring of pancreatic cancer patients. Compliance Whitings Sleep: compliance with daily sleep monitoring is calculated by the number of nights sleep is measured. A compliance rate of at least 75% nights per week will be considered as feasible.
Time frame: Through study completion, an average of 18 months
Trial@home monitoring related outcome: feasibility ePRO application
To assess the feasibility of the Trial@home monitoring via the ePRO application for home monitoring of pancreatic cancer patients. Compliance questionnaires through the ePROapplication: A compliance rate of at least 75% from the scheduled assessments will be considered as feasible.
Time frame: Through study completion, an average of 18 months
Trial@home monitoring related outcome: digital biomarkers
To exploratively generate digital biomarkers and quantify the correlation between data obtained from the Trial@home platform (Withings Steel HR smartwatch, a Withings Body+ Scale, a Withings Sleep, ePRO) and clinical endpoints (e.g., unplanned hospitalizations, early signs of adverse events, clinical deterioration, performance status, quality of life)
Time frame: Through study completion, an average of 18 months
Intervention arm related outcome toxicity
To assess acute (3 months) RT-related toxicity measured from the start of MRgRT, according to CTCAE v527
Time frame: Through study completion, an average of 18 months
Intervention arm related outcome, completion of therapy
To assess completion of therapy
Time frame: Through study completion, an average of 18 months
Intervention arm related outcome diffusion weighted images
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
Time frame: Through study completion, an average of 18 months