Preoperative, Proton- Radiotherapy Combined With Chemotherapy For Borderline Resectable Pancreatic Cancer

Study Overview

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

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.

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.

Pancreatic Cancer
Proton Therapy

RADIATION: Proton Ions
DRUG: Nab-PACLitaxel
DRUG: Gemcitabine
DRUG: Capecitabine
PROCEDURE: Surgical resection of the pancreas (when feasible)

PARC-MA-062019

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-05-10	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-05-07
First Submitted that Met QC Criteria 2021-05-17	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-05-08
First Posted (ACTUAL) 2021-05-20	Results First Posted N/A	Last Verified 2025-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Other

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

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 concomit	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. 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 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 che

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 concomit

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.

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

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 che

Primary Outcome Measures	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	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Piero Fossati, M.D.

Phone Number: +43 664 80878

Email: piero.fossati@medaustron.at

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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)

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Landesklinkum Wiener Neustadt

Investigators

PRINCIPAL_INVESTIGATOR: Piero Fossati, M.D., EBG MedAustron GmbH

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record