Surgery Versus Stereotactic Ablative Radiotherapy for Patients With Locally Advanced Pancreatic Cancer With Favourable Biological Response Following Induction Chemotherapy

NCT07867873 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 2026.0299 - NL-010805 - R03773
• Study Type: interventional
• Target: 230
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this study is to assess the added value of surgical exploration with intention for resection compared to MRI guided stereotactic ablative radiotherapy (SABR) in improving overall survival in patients with locally advanced pancreatic carcinoma (LAPC) who show a favourable biological response to systemic induction chemotherapy.

Conditions

Locally Advanced Pancreatic Carcinoma (LAPC)

Keywords

Locally advanced pancreatic carcinoma; surgery; radiotherapy; MRI-guided stereotactic ablative radiotherapy; stereotactic ablative radiotherapy

Outcome Measures

Primary Outcomes (1)

• Overall survival

  This will be measured in days. Participants receive systemic induction therapy before randomization, with a minimum duration of 3 months but no fixed duration. Therefore, overall survival is measured from the date of randomization.

  Measured from the date of randomization to the date of documented death by any cause or the date of last follow up, whichever occurs first, assessed up to at 5 years of randomization.

Secondary Outcomes (4)

• Failure free survival

  FFS is measured in days from date of randomization to date of first documented failure (whichever occurs first). Participants without documented failure will be censored at the date of last follow-up. FFS will be assessed up to 5yrs after randomization

• Quality of life

  First two years from randomization

• serious adverse events

  Six-months serious adverse events (SAEs) that occur from randomization

• Global quality of life

  First two years from randomization

Other Outcomes (4)

• in hospital/90 day major morbidity

  Measured from intervention until 90 days after intervention or discharge.

• in hospital/90 day clinically relevant pancreatic surgery specific complications

  Measured from surgery until 90 days after intervention or discharge.

• R0 resection rate

  Resection rate should be assessed by a pathologists within 2 weeks from pancreatic surgery

Study Arms (2)

Surgery

EXPERIMENTAL

Pancreatic surgery

Procedure: Pancreatic surgery

MRI guided stereotactic ablative radiotherapy

ACTIVE COMPARATOR

MRI guided stereotactic ablative radiotherapy

Radiation: MRI guided stereotactic ablative radiotherapy

Interventions

Pancreatic surgery PROCEDURE

Surgical exploration starts with a staging laparoscopy, unless already performed previsouly. Hereafter, exploration is typically performed via laparotomy. Although heterogeneity exist in surgical techniques, the following general surgical principles are considered state-of-the-art: 1. Artery-first approach in case of potential arterial involvement 2. Arterial divestment in case of radiological signs of (former) involvement without current signs of arterial wall ingrowth (and negative biopsy of peri-arterial tissue) during surgery to remove all (former) tumour tissue. 3. In case of vascular reconstruction that requires a patch or interposition graft, an autol-ogous (e.g., veins, peritoneal / falciform patch, splenic artery) or biological (e.g., bovine patch) graft is strongly preferred over synthetic prosthesis

Surgery

MRI guided stereotactic ablative radiotherapy RADIATION

MRI-guided SABR must be initiated within four weeks after randomization and is delivered in a hypofractioned regimen of 50 Gy in five fractions of 10 Gy, prescribed to 95% of the planning target volume (PTV). Treatment will be administered on alternative days, two or three times per week, with an intended overall treatment duration of two weeks (i.e., 14 days). All patients will undergo an MR (and CT scan at the department's discretion) for radiotherapy planning. The gross tumour volume (GTV) will be defined based on those imaging datasets and the restaging imaging. A PTV margin of 3mm is applied. Two MRI-guided SABR platforms are allowed. 1.5 Tesla MR-Linac and MRIdian system (0.35 Tesla MR-Linac). All patients will receive a proton pump inhibitor (oral) once daily during MRI-guided SABR, continued for three months afterwards to reduce gastrointestinal toxicity.

MRI guided stereotactic ablative radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: ≥18 years.
• Diagnosis:
• Anatomy:
• RECIST non-progressive disease on cross-sectional imaging;
• No radiological downstaging to a borderline resectable tumour;
• Surgical resection seems potentially feasible according to the local multidisciplinary team\*;
• Radiation is technically feasible according to the local multidisciplinary team;
• Biology:
• Serum CA19-9 reduction \>40% with an absolute end value \<300 U/mL after induction chemotherapy\*\*.
• NB1. If non-elevated serum CA19-9 at diagnosis, metabolic response on 18F-FDG PET scan defined as ≥30% reduction of SUVmax if \>4 at baseline#.
• NB2. If non-elevated serum CA19-9 at diagnosis\*\* and on 18F-FDG PET scan an SUVmax ≤4 at baseline, non-elevated serum CEA at restaging is required (i.e., ≤5 ng/ml).
• NB3. If serum CA19-9 after chemotherapy is \>150 U/ml, a negative staging laparoscopy is required prior to randomization (unless a staging laparoscopy was already performed prior to starting systemic therapy). This is based on the PREOPANC-4 cohort wherein such patients had a 23% risk of peritoneal metastases (vs. 5% with \<150 U/ml).
• Condition:
• ECOG/WHO performance status 0-1 at restaging, being fit for surgery and chemotherapy
• NB. If a systemic treatment switch is performed in the setting of induction therapy with the indication of (biochemical) disease progression, restaging according to the above-mentioned criteria are performed with using the A-B-C features between the first- and second-line systemic induction therapy as baseline.

You may not qualify if:

• \- Prior treatment: Prior systemic induction therapy combined with any type of radiother-apy. Radiotherapy is not used as induction therapy as it has not been proven beneficial and considering the potential increased risk of major morbidity, although particularly seen with external beam radiotherapy. The only other possible indication for radio-therapy that is allowed in this trial is a single fraction of 8 Gray in case of tumour bleed-ing.
• \- Metastatic disease: Presence of metastatic disease
• \- Comorbidities: Clinical deterioration during systemic induction therapy or increase of suspected tumour-related pain after excluding other potential causes of pain (e.g., pancreatitis, stent dysfunction).

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Erasmus Medical Center: collaborator
• University Hospital Verona, Italy: collaborator
• University Hospital Heidelberg: collaborator
• Catharina Ziekenhuis Eindhoven: collaborator
• St. Antonius Hospital: collaborator
• Leiden University Medical Center: collaborator
• Radboud University Medical Center: collaborator
• University Medical Center Groningen: collaborator
• Maastricht University Medical Center: collaborator
• San Raffaele University Hospital, Italy: collaborator
• West China Hospital: collaborator
• Institut Paoli-Calmettes: collaborator
• University Hospital, Essen: collaborator
• Copenhagen University Hospital, Denmark: collaborator
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: collaborator
• University Hospital Padova: collaborator
• University Hospital Ulm: collaborator
• Assistance Publique - Hôpitaux de Paris: collaborator
• Ruijin Hospital: collaborator
• Tubingen University Hospital: collaborator

Study Officials

• Sterre de Vet, MD, Phd

  AmsterdamUMC

  STUDY DIRECTOR

• Floor Fabels, Md, Phd

  EramusMC

  STUDY DIRECTOR

Central Study Contacts

Marc Besselink, Prof. MD, Phd, surgeon

CONTACT

+31616767330; m.g.besselink@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof, MD, Phd, surgeon

Study Record Dates

• First Submitted: September 8, 2026
• First Posted: October 9, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2034
• Study Completion (Estimated): October 1, 2034
• Last Updated: October 9, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share