Locally Advanced Pancreatic Cancer After Systemic Therapy: Ablative MR-guided Radiotherapy

NCT ID: NCT06272162

Last Updated: 2024-02-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-29
• Study Completion Date: 2030-01-31

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.

Conditions

Locally Advanced Pancreatic Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention arm

Patients in the intervention arm will receive locally ablative stereotactic MRgRT in addition to standard of care, consisting of 5 times 10 Gy MR guided radiotherapy.

Group Type: EXPERIMENTAL

MR guided radiotherapy

Intervention Type: RADIATION

5 fractions of 10 Gray MRgRT in addition to standard of care

Control arm

Patients randomized to the control arm will continue standard of care as described without additional local treatment.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

MR guided radiotherapy

5 fractions of 10 Gray MRgRT in addition to standard of care

Intervention Type: RADIATION

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

Catharina Ziekenhuis Eindhoven

OTHER

Sponsor Role: collaborator

Centre for Human Drug Research, Netherlands

OTHER

Sponsor Role: collaborator

Dutch Pancreatic Cancer Group (DPCG)

UNKNOWN

Sponsor Role: collaborator

UMC Utrecht

OTHER

Sponsor Role: lead

Responsible Party

Lois Daamen

Prinipal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

L. A. Daamen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Regional Academic Cancer Center Utrecht (RACU)

M P.W. Intven, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Regional Academic Cancer Center Utrecht (RACU)

A. M.E. Bruynzeel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam University Medical Center, VUmc

H. D. Heerkens, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

H. M.U. Peulen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Catharina Ziekenhuis Eindhoven

J. J. Bosch

Role: PRINCIPAL_INVESTIGATOR

Centre of Human Drug Research

Locations

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

Countries

Netherlands

Central Contacts

Lois Daamen, MD, PhD

Role: CONTACT

L.a.daamen-3@umcutrecht.nl

+ 316 51223276

Jacobien Scheepens, MD

Role: CONTACT

j.c.m.scheepens-7@umcutrecht.nl

+31 6 21477044

Facility Contacts

J. C.M. Scheepens, MD

Role: primary

j.c.m.scheepens-7@umcutrecht.nl

J. C.M. Scheepens, MD

Role: primary

j.c.m.scheepens-7@umcutrecht.nl

J. C.M. Scheepens, MD

Role: primary

j.c.m.scheepens-7@umcutrecht.nl

J. C.M. Scheepens, MD

Role: primary

j.c.m.scheepens-7@umcutrecht.nl

Other Identifiers

15030

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

23U-0725

Identifier Type: OTHER

Identifier Source: secondary_id

NL85622.041.24

Identifier Type: -

Identifier Source: org_study_id