Clinical trial NCT04894643: Preoperative, Proton- Radiotherapy Combined With Chemotherapy for Borderline Resectable Pancreatic Cancer
Official title: Preoperative, Proton- Radiotherapy Combined With Chemotherapy for Borderline Resectable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pancreatic Cancer
Proton Therapy
Keywords: Proton therapy combined with chemotherapy
Borderline Resectable Pancreatic Cancer
Lead sponsor: EBG MedAustron GmbH
Sponsor class: INDUSTRY
Collaborators: name: Landesklinkum Wiener Neustadt
First posted: 2021-05-20
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a 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
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Toxicity - Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
timeFrame: from enrollment to six months after surgery
measure: Perioperative Mortality and Complications
timeFrame: 90 days postoperatively
Secondary outcomes:
measure: Toxicity - CTCAE v5.0
timeFrame: from enrollment to six months after surgery
measure: Tumor recurrence
timeFrame: 260 weeks after therapy
measure: Progression free survival
timeFrame: 260 weeks after therapy
measure: Overall survival
timeFrame: 282 weeks
measure: Pathologic tumor response
timeFrame: 260 weeks
measure: Radiologic response
timeFrame: 263 weeks after proton therapy
measure: Quality of Life questionnaire: Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep)
timeFrame: 282 weeks
measure: Quality of Life questionnaire: European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-30)
timeFrame: 282 weeks
measure: Quality of Life questionnaire: Brief Pain Inventory
timeFrame: 282 weeks
Other outcomes:
Locations:
city: Wiener Neustadt
country: Austria
facility: EBG MedAustron GmbH
state: Niederösterreich
city: Wiener Neustadt
country: Austria
facility: Department of Surgery, LK Wiener Neustadt
Study officials:
affiliation: EBG MedAustron GmbH
name: Piero Fossati, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: LK Wiener Neustadt, Department of Surgery
name: Friedrich Längle, Prim., Univ. Doz., M.D.
role: PRINCIPAL_INVESTIGATOR
References: