Preoperative, Proton- Radiotherapy Combined With Chemotherapy for Borderline Resectable Pancreatic Cancer (PARC)

This is an interventional, single arm, open-label, feasibility trial with gemcitabine and nab-paclitaxel, followed by concomitant proton therapy and capecitabine, followed by re-evaluation and surgery (when feasible) for patients with borderline resectable pancreatic cancer.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; Proton Therapy
• Intervention / Treatment: Radiation: Proton Ions; Drug: Nab-PACLitaxel; Drug: Gemcitabine; Drug: Capecitabine; Procedure: Surgical resection of the pancreas (when feasible)

Detailed Description

This is an interventional, single arm, open label, feasibility trial of preoperative chemotherapy + concomitant chemo-proton therapy followed by surgery (when feasible) for patients with borderline resectable pancreatic cancer. Aim of this study is to test referral and enrollment procedures as well as technical feasibility. Proton therapy will be delivered in MedAustron, which is a stand alone facility. Pancreatic cancer patients are typically complex cases that require multidisciplinary care. Moreover delivery of high dose of proton therapy to large volumes including the upper abdomen lymphnodes and pancreatic neural plexus is technically challenging, therefore a feasibility study is deemed necessary. Following this study, a larger study will be performed aiming to confirm the ability of preoperative chemotherapy + concomitant chemo-proton therapy to improve resectability and ultimately outcome of borderline resectable pancreatic cancer without increase in toxicity.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Piero Fossati, M.D.; Phone Number: 408 +43 664 80878; Email: piero.fossati@medaustron.at

Study Locations

• Austria
  • Wiener Neustadt, Austria, 2700
    • Recruiting
    • Department of Surgery, LK Wiener Neustadt
    • Contact: Friedrich Längle, Prim., Univ. Doz., M.D.; Phone Number: 2484 +43 2622 9004; Email: friedrich.laengle@wienerneustadt.lknoe.at
    • Principal Investigator: Friedrich Längle, Prim., Univ. Doz., M.D.
    • Sub-Investigator: Birgit Grünberger, Prim., Priv. Doz., M.D.
  • Lower Austria
    • Wiener Neustadt, Lower Austria, Austria, 2700
      • Recruiting
      • EBG MedAustron GmbH
      • Contact: Piero Fossati, M.D.; Phone Number: 408 +43 2622 26 100; Email: piero.fossati@medaustron.at
      • Principal Investigator: Piero Fossati, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with histologically or cytologically confirmed diagnosis of pancreatic cancer
• Diagnosis of borderline resectable cancer according to the international consensus definition 2017.
• Negative staging for distant metastasis
• Blood test within the following limits absolute neutrophil count > 1,500 cells/mm³, platelet count > 100,000 cells/mm³, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 2.5 times the upper limit of normal, total bilirubin < 2.5 times the upper limit of normal if patient had recent biliary stenting, total bilirubin < 1.5 times the upper limit of normal if no biliary stenting was done, serum creatinine within normal range (0.6-1.5 mg/dl) with a creatinine clearance > 30 ml/min (as estimated by Cockroft Gault equation)
• Age > 18 years
• Karnofsky index ≥ 70
• No tumor infiltration of stomach or duodenum
• The patient is informed of the diagnosis and is able to give informed consent (Ability of subject to understand character and individual consequences of the study protocol)
• Women of fertile age must have adequate conception prevention measures and must not breast feed
• Signed Informed Consent (must be available before study inclusion)

Exclusion Criteria:

• Non-exocrine tumors
• Major medical or psychiatric comorbidities that contraindicate radiation therapy, chemotherapy or surgery
• Presence of distant metastasis
• Pregnancy or unwilling to do adequate conception prevention
• Lactating and unwilling to discontinue lactation
• Men of childbearing potential not willing to use effective means of contraception
• Known allergic/hypersensitivity reaction to any of the components of study treatments
• Previous diagnosis of another neoplasm with worse prognosis as compared with the one in this study
• Metallic prosthesis or other condition that prevent an adequate imaging for target volume definition
• Loco-regional conditions that contraindicate radiotherapy e.g. active infections in the area
• Previous abdominal radiotherapy
• Prior systemic treatment for pancreatic cancer
• Hypersensitivity to PACLitaxel, albumin, gemcitabine or to any of the excipients of the chemotherapy
• Severe hepatic impairment
• Baseline Neutrophil Counts < 1.5 x 10^9/L
• Baseline Grade ≥ 2 sensory or motor neuropathy
• Patient refusal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Preoperative, proton- radiotherapy combined with chemotherapy; Patients treated with three cycles of chemotherapy with Nab-PACLitaxel (Abraxane®) (125 mg/m² on day 1, 8, 15; powder for making a infusion solution) and Gemcitabine (1000 mg/m² on day 1, 8, 15; powder for making a infusion solution), followed by concomitant chemotherapy with capecitabine (1.660ml/m² on 5 days per week during the radiation therapy) and proton-therapy (with simultaneous integrated boost (SIB) 50.4 Gy Relative Biological Effectiveness (RBE) and 60.2 Gy (RBE) in 28 fractions of 1.8 Gy (RBE) and 2.15 Gy (RBE) 5 days per week), followed by re-evaluation and surgery

Radiation: Proton Ions; According to the radiation plan (between 50.4 and a maximum of 60.2 Gy) after Chemotherapy with Nab-PACLitaxel (Abraxane®) + Gemcitabine and concomitant to Capecitabine.; Drug: Nab-PACLitaxel; Chemotherapy will be delivered upfront for three cycles (week 2-4, week 6-8 and week 10-12) with combined Nab-PACLitaxel (Abraxane®) and Gemcitabine Therapy. It will be administered as intra venous infusion over 30 minutes.; Other Names: Abraxane®; Drug: Gemcitabine; Chemotherapy will be delivered upfront for three cycles (week 2-4, week 6-8 and week 10-12) with combined Nab-PACLitaxel (Abraxane®) and Gemcitabine Therapy. Gemcitabine will also be administered as intra venous infusion over 30 minutes immediately after Nab-PACLitaxel.; Drug: Capecitabine; Concomitant to proton-radiotherapy (on the same days, within week 14-19); Procedure: Surgical resection of the pancreas (when feasible); Pre surgical re-evaluation will be performed at week 21 after enrollment. Patients fulfilling surgery-entry criteria, which consist of no distant metastasis, no massive ascites, no massive pleural effusion, no serious infection, no serious, unresolved chemoradiotherapy related, adverse events and adequate organ system function, will undergo surgery on week 22 (± 1 week). This should be performed via laparotomy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity - Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Incidence of CTCAE version 5.0 Grade 4 non hematological toxicity from enrollment to six months after surgery	from enrollment to six months after surgery
Perioperative Mortality and Complications	Incidence of 90-days-perioperative mortality and incidence of Clavien Dindo Grade III complication rate during hospitalization	90 days postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity - CTCAE v5.0	CTCAE V5.0 toxicity from enrollment to six month after surgery	from enrollment to six months after surgery
Tumor recurrence	local and loco-regional (i.e. in-field) tumor recurrence	260 weeks after therapy
Progression free survival	loco-regional progression-free survival	260 weeks after therapy
Overall survival	Overall survival	282 weeks
Pathologic tumor response	Assessment of pathologic tumor response to pre-operative combined proton- chemotherapy (R0 margin and N0, degree of tumor cell necrosis in the resected tumor specimen)	260 weeks
Radiologic response	Assessment of radiologic response of pre-operative chemoradiotherapy. Response to preoperative treatment will be scored with the Japan Pancreas Society (JPS) classification which is a synthesis from the Evans and College of American Pathologists classification (Grade 1: poor or no response to Grade 4: complete response)	263 weeks after proton therapy
Quality of Life questionnaire: Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep)	Patient reported Quality of Life (for assessing disease-related symptoms and health-related quality of life). The higher the score the better the Quality of Life.	282 weeks
Quality of Life questionnaire: European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-30)	Questionnaire developed to assess the quality of life of cancer patients. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / quality of life (QoL) represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.	282 weeks
Quality of Life questionnaire: Brief Pain Inventory	The Brief Pain Inventory (BPI) is a measurement tool for assessing clinical pain.The interference items were now presented with 0-10 scales, with 0=no interference and 10=interferes completely.	282 weeks

Collaborators and Investigators

• Sponsor: EBG MedAustron GmbH
• Collaborators: Landesklinkum Wiener Neustadt
• Investigators: Principal Investigator: Piero Fossati, M.D., EBG MedAustron GmbH; Principal Investigator: Friedrich Längle, Prim., Univ. Doz., M.D., LK Wiener Neustadt, Department of Surgery

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 20, 2021

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Borderline Resectable Pancreatic Cancer; Proton therapy combined with chemotherapy
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Physical Phenomena; Inorganic Chemicals; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Elements; Nucleosides; Uracil; Pyrimidinones; Ions; Electrolytes; Deoxyribonucleosides; Fluorouracil; Gases; Elementary Particles; Albumins; Paclitaxel; Cations, Monovalent; Cations; Hydrogen; Nucleons; Capecitabine; Albumin-Bound Paclitaxel; Gemcitabine; 130-nm albumin-bound paclitaxel; Protons
• Other Study ID Numbers: PARC-MA-062019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No