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

Pancreatic Cancer Clinical Trial

— PARC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04894643
• Other study ID #: PARC-MA-062019
• Status: Recruiting
• Phase: N/A
• Start date: September 14, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: EBG MedAustron GmbH
• Contact: Piero Fossati, M.D.
• Phone: +43 664 80878
• Email: piero.fossati[@]medaustron.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms
• Proton Therapy

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Austria	Department of Surgery, LK Wiener Neustadt	Wiener Neustadt
Austria	EBG MedAustron GmbH	Wiener Neustadt	Niederösterreich

Sponsors (2)

Lead Sponsor	Collaborator
EBG MedAustron GmbH	Landesklinkum Wiener Neustadt

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Toxicity - CTCAE v5.0	CTCAE V5.0 toxicity from enrollment to six month after surgery	from enrollment to six months after surgery
Secondary	Tumor recurrence	local and loco-regional (i.e. in-field) tumor recurrence	260 weeks after therapy
Secondary	Progression free survival	loco-regional progression-free survival	260 weeks after therapy
Secondary	Overall survival	Overall survival	282 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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