Intraoperative Radiation Therapy For Resectable Pancreas Cancer

Study Overview

Intraoperative Radiation Therapy for Resectable Pancreas Cancer

Currently, for patients with pancreatic cancer the standard treatment is surgery followed by chemotherapy and/or radiation therapy. An investigational approach is to perform the surgery and treat the area of the tumor with intraoperative radiotherapy in one procedure. Intraoperative radiation delivers low energy x-rays to a targeted area during the time of tumor removal. The purpose of this study is to learn about both the good and bad effects of adding intraoperative radiation therapy. Another goal is to determine and compare the quality of life before and after the procedure. We will also monitor the effect of the therapy on the cancer lesion and any complications that may result.

The purpose of this study is to determine safety of low kilovoltage radiotherapy delivery of a focused dose of radiation to the areas at high risk for locoregional recurrence following pancreaticoduodenectomy. This surgery is currently the only potentially curative approach for patients with pancreatic cancer. Unfortunately, following surgery alone >50% of patients will have a local recurrence of disease [5]. Local control will become increasingly important as chemotherapy regimens continue to improve the distant metastases-free survival. Intraoperative radiation therapy allows direct access to the tumor bed and areas of concern while allowing displacement and shielding of normal tissue and organs at risk of radiation toxicity. Study Objectives The primary objective is to determine the maximum tolerated dose (MTD) for low kilovoltage (kV) intraoperative radiotherapy (IORT) The secondary objectives are: To develop acute and chronic toxicity profiles for this treatment modality To determine the feasibility of including low-kV IORT in the treatment of pancreatic cancer To evaluate the following physics and delivery parameters: treatment prescription dose, depth of treatment, applicator type, and treatment time. To measure patient's quality of life (QOL) before and after treatment, including change in pain level and fatigue level. To describe the disease specific outcomes of local regional control, progression free-survival, distant metastasis free-survival, disease free-survival and overall survival associated with low-kV IORT following pancreaticoduodenectomy.

Pancreas Cancer

RADIATION: 10 Gy Low-KV IORT
RADIATION: 15 Gy Low-KV IORT
RADIATION: 20 GY Low-KV IORT

207194
20719412115 (OTHER Identifier) (OTHER: Loyola University IRB)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-11-05	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-06-03
First Submitted that Met QC Criteria 2015-11-05	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-06-04
First Posted (ACTUAL) 2015-11-06	Results First Posted N/A	Last Verified 2020-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
OTHER: Group 1: 10 Gy Low-KV IORT 10 Gy Low Kilovoltage Intraoperative Radiation: intraoperative low-kV IORT will be delivered as a single dose of 10 Gy at 2 millimeter depth. Doses will be escalated in increments of 5 Gy until completion of 20 Gy dose level or the DLT is reached and MTD	RADIATION: 10 Gy Low-KV IORT : intraoperative low-kV IORT will be delivered as a single dose of 10 Gy at 2 millimeter depth. Doses will be escalated in increments of 5 Gy until completion of 20 Gy dose level or the DLT is reached and MTD is realized.
OTHER: Group 2: 15 Gy Low-KV IORT 15 Gy Low Kilovoltage Intraoperative Radiation: intraoperative low-kV IORT will be delivered as a single dose of 15 Gy at 2 millimeter depth. Doses will be escalated in increments of 5 Gy until completion of 20 Gy dose level or the DLT is reached and MTD	RADIATION: 15 Gy Low-KV IORT intraoperative low-kV IORT will be delivered as a single dose of 15 Gy at 2 millimeter depth. Doses will be escalated in increments of 5 Gy until completion of 20 Gy dose level or the DLT is reached and MTD is realized.
OTHER: Group 3: 20 GY Low-KV IORT 20 GY Low Kilovoltage Intraoperative Radiation: intraoperative low-kV IORT will be delivered as a single dose of 20 Gy at 2 millimeter depth. Patients will be accrued to this group until the DLT is reached and MTD is realized.	RADIATION: 20 GY Low-KV IORT intraoperative low-kV IORT will be delivered as a single dose of 20 Gy at 2 millimeter depth. Patients will be accrued to this group until the DLT is reached and MTD is realized.

Participant Group/Arm

Intervention/Treatment

OTHER: Group 1: 10 Gy Low-KV IORT

10 Gy Low Kilovoltage Intraoperative Radiation: intraoperative low-kV IORT will be delivered as a single dose of 10 Gy at 2 millimeter depth. Doses will be escalated in increments of 5 Gy until completion of 20 Gy dose level or the DLT is reached and MTD

RADIATION: 10 Gy Low-KV IORT

: intraoperative low-kV IORT will be delivered as a single dose of 10 Gy at 2 millimeter depth. Doses will be escalated in increments of 5 Gy until completion of 20 Gy dose level or the DLT is reached and MTD is realized.

OTHER: Group 2: 15 Gy Low-KV IORT

15 Gy Low Kilovoltage Intraoperative Radiation: intraoperative low-kV IORT will be delivered as a single dose of 15 Gy at 2 millimeter depth. Doses will be escalated in increments of 5 Gy until completion of 20 Gy dose level or the DLT is reached and MTD

RADIATION: 15 Gy Low-KV IORT

intraoperative low-kV IORT will be delivered as a single dose of 15 Gy at 2 millimeter depth. Doses will be escalated in increments of 5 Gy until completion of 20 Gy dose level or the DLT is reached and MTD is realized.

OTHER: Group 3: 20 GY Low-KV IORT

20 GY Low Kilovoltage Intraoperative Radiation: intraoperative low-kV IORT will be delivered as a single dose of 20 Gy at 2 millimeter depth. Patients will be accrued to this group until the DLT is reached and MTD is realized.

RADIATION: 20 GY Low-KV IORT

intraoperative low-kV IORT will be delivered as a single dose of 20 Gy at 2 millimeter depth. Patients will be accrued to this group until the DLT is reached and MTD is realized.

Primary Outcome Measures	Measure Description	Time Frame
Maximum Tolerated Dose	Maximum Tolerated Dose as defined by Radiation-related acute Grade 3-5 toxicity in greater than or equal to 2 patients out of 6 patients at any dose level	52 weeks

Secondary Outcome Measures	Measure Description	Time Frame
QOL surveys	. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQC30) 30 item questionnaire to evaluate cancer patients' physical, psychological, and social functioning. Patients are asked to rate symptoms on a YES or NO scale; a 4 point scale ranging from 1 (Not at all) to 4 (Very much); and a 7 point scale ranging 1 (Very poor) to 7 (Excellent)	52 weeks

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Beth Chiappetta, BSN

Phone Number: 708-216-2568

Email: bchiappetta@lumc.edu

Study Contact Backup

Name: Tarita Thomas, MD, PhD

Phone Number: 708-216-2571

Email: tathomas@lumc.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Pathologically confirmed pancreatic adenocarcinoma.
Age ≥ 18 years.
Performance status ECOG 0-1.
Patient must have resectable disease. In order to be resectable the following criteria must be met:
Absence of distant metastases.
Clear fat planes around the celiac axis, hepatic artery, and superior mesenteric artery .
Absence of direct involvement of inferior vena cava or aorta.
Stage I and stage II disease per AJCC 7th edition.
Complete history and physical examination including weight and ECOG performance status within 31 days of entry.
Laboratory data obtained ≤ 14 days prior to registration on study, with adequate bone marrow and organ function defined as follows:

Negative serum pregnancy test for females of childbearing potential within 14 days of study registration. Should a female participant become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone tubal ligation, or remaining celibate by choice) who meets the following criteria:

Has not undergone a hysterectomy or bilateral oophorectomy; or
Has not been naturally postmenopausal for at least 12 consecutive months.
Abdominal CT scan with contrast prior to performance of surgery. If patient is allergic to contrast an abdominal MRI may substitute. Other imaging may be added or substituted as deemed appropriate by the treatment team (surgeon, radiation oncologist, medical oncologist).
Ability to understand and the willingness to sign a written informed consent.
Signed study specific informed consent.
Patients with prior history of malignancy are permitted to register in the study as long as they are not actively taking cytotoxic or biologic medication for treatment of the prior malignancy. Patient must be disease-free from any malignancy for at least the previous 6 months and must have no history of brain metastases.
Consultation, agreement, and documentation by a radiation oncologist that the patient is suitable to receive radiotherapy per this protocol.
Consultation, agreement, and documentation by surgeon that the patient is a suitable surgical candidate.
Consultation, agreement, and documentation by an anesthesiologist that patient is suitable to receive general anesthesia.

Defined treatment area which cannot be adequately covered by the radiation field as defined by the radiation oncology treatment team.
Patients who have received neoadjuvant chemotherapy are ineligible.
Patients with Stage III-Stage IV disease.
Patients who have been on an immunosuppressive agent (excluding corticosteroids) within 4 weeks of the proposed operation.
Patients receiving any other investigational agents.
Current pregnancy or currently nursing.
History of brain metastases.
Severe, active comorbidity defined as follows
Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months. [23]
Myocardial infarction within 3 months of study registration [23].
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
Chronic Obstructive Pulmonary Disease or other respiratory illness hospitalization or precluding study therapy at time of registration [23].
Uncontrolled diabetes which in the opinion of any of the patient's physicians requires an immediate change in management. A patient may be considered eligible if the patient's physician managing the diabetes deems the appropriate changes in management have resulted in adequate control. [23].
BMI >30.
Patient with active diagnosis of a bleeding disorder. [23]
Patients enrolled in another interventional clinical trial.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan;63(1):11-30. doi: 10.3322/caac.21166. Epub 2013 Jan 17.
Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985 Aug;120(8):899-903. doi: 10.1001/archsurg.1985.01390320023003.
Mohammed S, Van Buren G 2nd, Fisher WE. Pancreatic cancer: advances in treatment. World J Gastroenterol. 2014 Jul 28;20(28):9354-60. doi: 10.3748/wjg.v20.i28.9354.
Nagakawa T, Kayahara M, Ohta T, Ueno K, Konishi I, Miyazaki I. Patterns of neural and plexus invasion of human pancreatic cancer and experimental cancer. Int J Pancreatol. 1991 Oct;10(2):113-9. doi: 10.1007/BF02924114.
Gnerlich JL, Luka SR, Deshpande AD, Dubray BJ, Weir JS, Carpenter DH, Brunt EM, Strasberg SM, Hawkins WG, Linehan DC. Microscopic margins and patterns of treatment failure in resected pancreatic adenocarcinoma. Arch Surg. 2012 Aug;147(8):753-60. doi: 10.1001/archsurg.2012.1126.
Iqbal N, Lovegrove RE, Tilney HS, Abraham AT, Bhattacharya S, Tekkis PP, Kocher HM. A comparison of pancreaticoduodenectomy with extended pancreaticoduodenectomy: a meta-analysis of 1909 patients. Eur J Surg Oncol. 2009 Jan;35(1):79-86. doi: 10.1016/j.ejso.2008.01.002. Epub 2008 Mar 19.
Hiraoka T. Extended radical resection of cancer of the pancreas with intraoperative radiotherapy. Baillieres Clin Gastroenterol. 1990 Dec;4(4):985-93. doi: 10.1016/0950-3528(90)90031-b. No abstract available.
Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. doi: 10.1056/NEJMoa1011923.
Wood WC, Shipley WU, Gunderson LL, Cohen AM, Nardi GL. Intraoperative irradiation for unresectable pancreatic carcinoma. Cancer. 1982 Mar 15;49(6):1272-5. doi: 10.1002/1097-0142(19820315)49:63.0.co;2-e.
Shipley WU, Wood WC, Tepper JE, Warshaw AL, Orlow EL, Kaufman SD, Battit GE, Nardi GL. Intraoperative electron beam irradiation for patients with unresectable pancreatic carcinoma. Ann Surg. 1984 Sep;200(3):289-96. doi: 10.1097/00000658-198409000-00006.
Kawai M, Yamaue H. Analysis of clinical trials evaluating complications after pancreaticoduodenectomy: a new era of pancreatic surgery. Surg Today. 2010 Nov;40(11):1011-7. doi: 10.1007/s00595-009-4245-9. Epub 2010 Nov 3.
Parikh P, Shiloach M, Cohen ME, Bilimoria KY, Ko CY, Hall BL, Pitt HA. Pancreatectomy risk calculator: an ACS-NSQIP resource. HPB (Oxford). 2010 Sep;12(7):488-97. doi: 10.1111/j.1477-2574.2010.00216.x.
Lermite E, Sommacale D, Piardi T, Arnaud JP, Sauvanet A, Dejong CH, Pessaux P. Complications after pancreatic resection: diagnosis, prevention and management. Clin Res Hepatol Gastroenterol. 2013 Jun;37(3):230-9. doi: 10.1016/j.clinre.2013.01.003. Epub 2013 Feb 14.

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