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

Primary Purpose

Pancreatic Cancer, Proton Therapy

Status

Recruiting

Phase

Not Applicable

Locations

Austria

Study Type

Interventional

Intervention

Proton Ions

Nab-PACLitaxel

Gemcitabine

Capecitabine

Surgical resection of the pancreas (when feasible)

About this trial

This is an interventional other trial for Pancreatic Cancer focused on measuring Proton therapy combined with chemotherapy, Borderline Resectable Pancreatic Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

EBG MedAustron GmbHRecruiting
Department of Surgery, LK Wiener NeustadtRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Preoperative, proton- radiotherapy combined with chemotherapy

Arm 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

Outcomes

Primary Outcome Measures

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

Perioperative Mortality and Complications

Incidence of 90-days-perioperative mortality and incidence of Clavien Dindo Grade III complication rate during hospitalization

Secondary Outcome Measures

Toxicity - CTCAE v5.0

CTCAE V5.0 toxicity from enrollment to six month after surgery

Tumor recurrence

local and loco-regional (i.e. in-field) tumor recurrence

Progression free survival

loco-regional progression-free survival

Overall survival

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)

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)

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.

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.

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.

Full Information

NCT ID

NCT04894643

First Posted

May 10, 2021

Last Updated

January 25, 2023

Sponsor

EBG MedAustron GmbH

Collaborators

Landesklinkum Wiener Neustadt

1. Study Identification

Unique Protocol Identification Number

NCT04894643

Brief Title

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

Acronym

PARC

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 14, 2020 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

EBG MedAustron GmbH

Collaborators

Landesklinkum Wiener Neustadt

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Cancer, Proton Therapy

Keywords

Proton therapy combined with chemotherapy, Borderline Resectable Pancreatic Cancer

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

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

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Preoperative, proton- radiotherapy combined with chemotherapy

Arm Type

Other

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Proton Ions

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Nab-PACLitaxel

Other Intervention Name(s)

Abraxane®

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Capecitabine

Intervention Description

Concomitant to proton-radiotherapy (on the same days, within week 14-19)

Intervention Type

Procedure

Intervention Name(s)

Surgical resection of the pancreas (when feasible)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Toxicity - Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Description

Incidence of CTCAE version 5.0 Grade 4 non hematological toxicity from enrollment to six months after surgery

Time Frame

from enrollment to six months after surgery

Title

Perioperative Mortality and Complications

Description

Incidence of 90-days-perioperative mortality and incidence of Clavien Dindo Grade III complication rate during hospitalization

Time Frame

90 days postoperatively

Secondary Outcome Measure Information:

Title

Toxicity - CTCAE v5.0

Description

CTCAE V5.0 toxicity from enrollment to six month after surgery

Time Frame

from enrollment to six months after surgery

Title

Tumor recurrence

Description

local and loco-regional (i.e. in-field) tumor recurrence

Time Frame

260 weeks after therapy

Title

Progression free survival

Description

loco-regional progression-free survival

Time Frame

260 weeks after therapy

Title

Overall survival

Description

Overall survival

Time Frame

282 weeks

Title

Pathologic tumor response

Description

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)

Time Frame

260 weeks

Title

Radiologic response

Description

Time Frame

263 weeks after proton therapy

Title

Quality of Life questionnaire: Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep)

Description

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.

Time Frame

282 weeks

Title

Quality of Life questionnaire: European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-30)

Description

Time Frame

282 weeks

Title

Quality of Life questionnaire: Brief Pain Inventory

Description

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.

Time Frame

282 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Piero Fossati, M.D.

Phone

+43 664 80878

Ext

408

piero.fossati@medaustron.at

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Piero Fossati, M.D.

Organizational Affiliation

EBG MedAustron GmbH

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Friedrich Längle, Prim., Univ. Doz., M.D.

Organizational Affiliation

LK Wiener Neustadt, Department of Surgery

Official's Role

Principal Investigator

Facility Information:

Facility Name

EBG MedAustron GmbH

City

Wiener Neustadt

State/Province

Niederösterreich

ZIP/Postal Code

2700

Country

Austria

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Piero Fossati, M.D.

Phone

+43 2622 26 100

Ext

408

piero.fossati@medaustron.at

First Name & Middle Initial & Last Name & Degree

Piero Fossati, M.D.

Facility Name

Department of Surgery, LK Wiener Neustadt

City

Wiener Neustadt

ZIP/Postal Code

2700

Country

Austria

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Friedrich Längle, Prim., Univ. Doz., M.D.

Phone

+43 2622 9004

Ext

2484

friedrich.laengle@wienerneustadt.lknoe.at

First Name & Middle Initial & Last Name & Degree

Friedrich Längle, Prim., Univ. Doz., M.D.

First Name & Middle Initial & Last Name & Degree

Birgit Grünberger, Prim., Priv. Doz., M.D.

12. IPD Sharing Statement

Learn more about this trial

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

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