Clinical trial NCT06272162: Locally Advanced Pancreatic Cancer After Systemic Therapy: Ablative MR-guided Radiotherapy
Official title: Locally Advanced Pancreatic Cancer After Systemic Therapy: Ablative MR-guided Radiotherapy, a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Locally Advanced Pancreatic Adenocarcinoma
Keywords: MR guided radiation therapy
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Amsterdam UMC, location VUmc
name: Radboud University Medical Center
name: Catharina Ziekenhuis Eindhoven
name: Centre for Human Drug Research, Netherlands
name: Dutch Pancreatic Cancer Group (DPCG)
First posted: 2024-02-22
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: RCT
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: HRQoL deterioration-free survival
timeFrame: Through study completion, an average of 18 months
Secondary outcomes:
measure: Overall survival
timeFrame: From the date of LAPC diagnosis untill either death from any cause or last follow-up, whichever came first, assessed up to 18 months
measure: Patient reported Quality of Life EORTC QLQ-PAN26
timeFrame: At baseline and at 2,4, weeks and subsequently every 2 months. Assessed through study completion, up to 18 months
measure: Patient reported Quality of Life EORTC QLQ-C30
timeFrame: At baseline and at 2,4, weeks and subsequently every 2 months. Assessed through study completion, up to 18 months
measure: Patient reported Quality of Life EQ5D-5L
timeFrame: At baseline and at 2,4, weeks and subsequently every 2 months. Assessed through study completion, up to 18 months
measure: The need of subsequent treatments
timeFrame: Through study completion, an average of 18 months
measure: Treatment response assessed on CT-imaging (graded according to RECIST guidelines)
timeFrame: with available imaging during 18 months follow-up
measure: CA 19.9 response
timeFrame: Through study completion, an average of 18 months
measure: Trial@home monitoring related outcome: feasibility Withings Steel HR smartwatch
timeFrame: Through study completion, an average of 18 months
measure: Trial@home monitoring related outcome: feasibility Body+ scale
timeFrame: Through study completion, an average of 18 months
measure: Trial@home monitoring related outcome: feasibility Whitings Sleep
timeFrame: Through study completion, an average of 18 months
measure: Trial@home monitoring related outcome: feasibility ePRO application
timeFrame: Through study completion, an average of 18 months
measure: Trial@home monitoring related outcome: digital biomarkers
timeFrame: Through study completion, an average of 18 months
measure: Intervention arm related outcome toxicity
timeFrame: Through study completion, an average of 18 months
measure: Intervention arm related outcome, completion of therapy
timeFrame: Through study completion, an average of 18 months
measure: Intervention arm related outcome diffusion weighted images
timeFrame: Through study completion, an average of 18 months
Other outcomes:
Locations:
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
state: Noord- Brabant
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center, VUmc
state: Noord-Holland
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: Regional Academic Cancer Center Utrecht (RACU)
name: L. A. Daamen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Regional Academic Cancer Center Utrecht (RACU)
name: M P.W. Intven, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Amsterdam University Medical Center, VUmc
name: A. M.E. Bruynzeel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center
name: H. D. Heerkens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Catharina Ziekenhuis Eindhoven
name: H. M.U. Peulen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre of Human Drug Research
name: J. J. Bosch
role: PRINCIPAL_INVESTIGATOR
References: