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

Sponsor

EBG MedAustron GmbH (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04894643

Collaborator

Landesklinkum Wiener Neustadt (Other)

Enrollment

Locations

Arm

75.5

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer Proton Therapy	Radiation: Proton Ions Drug: Nab-PACLitaxel Drug: Gemcitabine Drug: Capecitabine Procedure: Surgical resection of the pancreas (when feasible)	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

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 cancerThis 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

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Sep 14, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Toxicity - CTCAE v5.0 [from enrollment to six months after surgery]
CTCAE V5.0 toxicity from enrollment to six month after surgery
Tumor recurrence [260 weeks after therapy]
local and loco-regional (i.e. in-field) tumor recurrence
Progression free survival [260 weeks after therapy]
loco-regional progression-free survival
Overall survival [282 weeks]
Overall survival
Pathologic tumor response [260 weeks]
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)
Radiologic response [263 weeks after proton therapy]
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)
Quality of Life questionnaire: Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) [282 weeks]
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.
Quality of Life questionnaire: European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-30) [282 weeks]
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.
Quality of Life questionnaire: Brief Pain Inventory [282 weeks]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	EBG MedAustron GmbH	Wiener Neustadt	Niederösterreich	Austria	2700
2	Department of Surgery, LK Wiener Neustadt	Wiener Neustadt		Austria	2700

Sponsors and Collaborators

EBG MedAustron GmbH
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