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

EBG MedAustron

Status: Enrolling

Conditions: Proton Therapy; Pancreatic Cancer

Treatments: Procedure: Surgical resection of the pancreas (when feasible); Drug: Nab-PACLitaxel; Radiation: Proton Ions; Drug: Gemcitabine; Drug: Capecitabine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04894643

PARC-MA-062019

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Preoperative, proton- radiotherapy combined with chemotherapy

Other group

Description:

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

Treatment:

Drug: Capecitabine

Drug: Gemcitabine

Radiation: Proton Ions

Drug: Nab-PACLitaxel

Procedure: Surgical resection of the pancreas (when feasible)