Stereotactic Body Radiation Therapy for Inoperable Non-metastasized Pancreatic Adenocarcinoma

NCT06691425 | Recruiting

• 1 other identifier: CTO22014GZA
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 9

Brief Summary

This is a multicenter randomized phase II trial that aims to include 160 patients with a non-metastatic (localized), inoperable pancreatic tumor. The study will take place at multiple centers across Europe. The primary objective of the study is to demonstrate superiority in progression free survival (PFS) by adding stereotactic body radiation therapy (SBRT) to chemotherapy for patients with an inoperable non-metastasized pancreatic tumor. SBRT is a radiotherapy technique (i.e. destroying cancer cells by means of ionizing irradiation) in which tumors can be irradiated with a high radiation dose. Surrounding healthy tissue is thus spared to the maximum extent. The primary endpoint of the TORPEDO study is 2-year PFS defined as the percentage of patients who are free of disease progression at 110 weeks after the date when the patients were drawn into 2 treatment groups (i.e. randomization). Secondary outcomes are, among others, quality of life, acute and late toxicity (i.e. adverse events), metastasis-free survival, local progression-free survival, overall survival, subsequent resectability, R0 resection and surgical morbidity. During the study, patients without disease progression after 3 months of induction chemotherapy will be randomized 1:1 to either treatment with chemotherapy or treatment with a combination of chemotherapy and SBRT (5 x 8 Gy). After randomization, ten-weekly follow-up visits will occur during two years to evaluate the quality of life, general blood parameters and general health condition of the patient. Moreover, toxicity will be evaluated as well as efficiency and safety of the treatment (e.g. by means of imaging). At any time during this follow-up period, imaging (CT scan, MRI scan) will be used to determine whether surgery can still be performed to improve patient survival.

Conditions

Non-metastasized Unresectable Pancreatic Carcinoma

Keywords

Pancreatic cancer; Randomized; stereotactic body radiation therapy; inoperable; non-metastasized

Outcome Measures

Primary Outcomes (1)

• 2-year progression-free survival

  2-year progression-free survival (PFS): defined as the percentage of patients who are free of disease progression at 110 weeks (+/- 1 week) after the date of randomization. Events considered as progression are: * Disease progression per RECIST 1.1 with the exception of cases determined as pseudoprogression at the first response assessment (i.e. at 10w +/- 1w after randomization). * Discovery of hepatic or peritoneal carcinomatosis during surgical exploration * Recurrent disease following R0/R1 resection * Death due to any cause

  From randomization until 110 weeks (+/- 1 week) after the date of randomization, assessed up to 110 weeks (+/- 1 week).

Secondary Outcomes (13)

• Metastasis-free survival (MFS)

  Measured from the date of randomization to time of distant metastasis, assessed up to 110 weeks (+/- 1 week)

• Local progression-free survival (LPFS)

  Measured from the date of randomization to locoregional progression, assessed up to 110 weeks (+/- 1 week).

• Overall survival (OS)

  Measured from the date of randomization to the date of death or last known follow-up date, assessed up to 6 years

• R0 resection rate

  Measured at the moment surgery took place (if surgery took place)

• Acute and late toxicity

  From signing ICF until 110 weeks (+/- 1 week) after randomization, assessed up to approximately 2.5 years

Study Arms (2)

Arm A: Chemotherapy alone

ACTIVE COMPARATOR

Patients in arm A will receive standard treatment, more specifically chemotherapy (mFOLFIRINOX or Gemcitabine/nab-paclitaxel) alone. After the 12 weeks of induction chemotherapy followed by randomization, these patients will receive further chemotherapy. A maximal total duration of 24 weeks of chemotherapy (including induction chemotherapy) will be administered for patients in arm A undergoing R0/R1 resection. Duration of chemotherapy for patients in arm A not undergoing R0/R1 resection is left at the discretion of the treating physician.

Drug: Chemotherapy

Arm B: Chemotherapy with SBRT

EXPERIMENTAL

Patients in arm B will receive SBRT in addition to chemotherapy (mFOLFIRINOX or Gemcitabine/nab-paclitaxel). After the 12 weeks of induction chemotherapy followed by randomization, these patients will receive another month of chemotherapy. Fiducial markers are implanted (unless MR LINAC is used to deliver radiotharapy) prior to the administration of SBRT, which will start 14 days (+/- 1 week) after either the first day of the eighth cycle of mFOLFIRINOX or the fifteenth day of the fourth cycle of Gemcitabine/nab-paclitaxel. 5 fractions of 8 Gy will be delivered. SBRT is preferably followed by further chemotherapy. The maximal total duration of chemotherapy for these patients is 24 weeks.

Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: Chemotherapy

Interventions

Stereotactic Body Radiation Therapy (SBRT) RADIATION

SBRT (5 x 8 Gy)

Arm B: Chemotherapy with SBRT

Chemotherapy DRUG

Standard of care: mFOLFIRINOX or gemcitabine/nab-paclitaxel

Arm A: Chemotherapy alone; Arm B: Chemotherapy with SBRT

Eligibility Criteria

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

You may qualify if:

• Participant must be over 18 years of age.
• Participant is able and willing to provide written informed consent which includes compliance with and ability to undergo all study procedures and attend the scheduled follow-up visits per protocol.
• Either locally advanced or borderline resectable pancreatic adenocarcinoma, as confirmed by diagnostic images (CT, MRI or PET-CT scan) and based on vessel involvement according to the NCCN guidelines. Only borderline resectable pancreatic cancer (BRPC) patients who are medically unfit for surgery or refusing surgery can be included.
• Adequate organ function determined by the following laboratory values:
• Adequate bone marrow function: absolute neutrophil count ≥1500/mm\^3, platelet count ≥100000/mm\^3 and hemoglobin ≥9 g/dl
• Adequate renal function: Creatinine ≤1.5 x upper normal limit of normal (ULN) or estimated eGFR more than 45 ml/min
• Adequate liver function: total bilirubin ≤1.5 ULN (after adequate biliairy stenting with metal stent) and alanine aminotransferase (ALT) ≤5x ULN
• An Eastern Cooperative Oncology Group (ECOG) performance status grade of 0-2.
• A life expectancy ≥3 months
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
• Is not a woman of child bearing potential or
• A woman of child bearing potential must have a negative serum pregnancy test at screening and must use a very effective method of birth control.

You may not qualify if:

• Extrapancreatic metastatic disease as defined on diagnostic imaging (CT, MRI or PET-CT scan) or laparoscopy, including distal nodal involvement beyond the peripancreatic tissues and/or distant metastases.
• Massive gastric or intestinal invasion as assessed on imaging and/or endoscopy. Direct invasion of the duodenal mucosa as visible on endoscopic ultrasound (EUS).
• Prior radiation therapy that could hamper adequate dose delivery
• Contraindication to magnetic resonance imaging (MRI)
• Diagnosis of another malignancy within 2 years prior to randomization, except non-melanoma skin cancer, non-invasive bladder cancer, carcinoma in situ of the cervix or non-metastatic prostate cancer. Patients with a history of other malignancies are eligible if they have been continuously disease-free for at least 2 years after definitive primary treatment.
• Any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the subject.
• Patient already included in another clinical trial that would interfere with the TORPEDO clinical trial, as assessed by the Investigator.
• Known presence of an active ulcer (i.e. detected during standard of care diagnostic assessments)
• Extrapancreatic metastatic disease as defined on diagnostic imaging, including distal nodal involvement beyond the peripancreatic tissues and/or distant metastases
• Massive gastric or intestinal invasion as assessed on imaging and/or endoscopy. Direct invasion of the duodenal mucosa as visible on EUS.
• Known presence of an active ulcer (i.e. detected during standard of care diagnostic assessments)

Sponsors & Collaborators

• Cancer Research Antwerp: lead
• Kom Op Tegen Kanker: collaborator
• Naslund Medical AB: collaborator
• Varian Medical Systems: collaborator

Study Sites (9)

UZA

Edegem, Antwerpen, 2650, Belgium

RECRUITING

ZAS Augustinus

Wilrijk, Antwerp, 2610, Belgium

RECRUITING

AZ Klina

Brasschaat, 2930, Belgium

RECRUITING

AZ Sint-Jan

Bruges, 8000, Belgium

RECRUITING

ZOL

Genk, 3600, Belgium

RECRUITING

Jessa ziekenhuis

Hasselt, 3500, Belgium

RECRUITING

AZ Groeninge

Kortrijk, 8500, Belgium

RECRUITING

AZ Delta

Roeselare, 8800, Belgium

RECRUITING

AZ Turnhout

Turnhout, 2300, Belgium

RECRUITING

Related Publications (1)

• Stas D, Vandamme T, Roeyen G, Reynders D, Demey W, Stellamans K, Bussels B, Hutsebaut I, Maurissen I, Bouchart C, Berbee M, Lallemand F, Poels H, Thomas M, Cuyle PJ, Bulens P, Verboven K, Martens M, Weytjens R, Joye I. Stereotactic body radiation therapy for inoperable non-metastasized pancreatic adenocarcinoma: a randomised phase II study (TORPEDO). BMC Cancer. 2025 Oct 30;25(1):1671. doi: 10.1186/s12885-025-15041-8.

  PMID: 41168707 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Radiosurgery; Drug Therapy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Ines Joye, MD, PhD

CONTACT

034433759; gza.cancertrials@zas.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2024
• First Posted: November 15, 2024
• Study Start: July 19, 2024
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2030
• Last Updated: August 8, 2025

Record last verified: 2025-08

Locations

BE (9)