MR Guided Phase II Radiotherapy Dose Escalation in Unresectable Non-Metastatic Pancreatic Cancer

MR Guided Phase II Radiotherapy Dose Escalation in Unresectable Non-metastatic Pancreatic Cancer

This research study is for people who have pancreas cancer for which surgery is not recommended. Potential patients must have already received several months of chemotherapy before they are eligible for this study and there will not have been any detectable spread of their tumor on imaging studies following this chemotherapy course.

Study Overview

• Status: Active, not recruiting
• Conditions: Unresectable Pancreatic Cancer
• Intervention / Treatment: Radiation: Radiation Therapy; Drug: Concurrent chemotherapy (Gemcitabine, Capecitabine)

Detailed Description

In this study the investigators want to find out more about the efficacy of giving higher doses of radiation with concurrent chemotherapy in controlling unresectable pancreas cancers than are used in either the pre-operative or post-operative setting. The investigators will assess acute and late side effects (problems and symptoms) of radiation therapy given at these higher doses of radiation (dose escalated) following full dose chemotherapy given before the radiation and with concurrent chemotherapy for pancreas cancer. Radiation therapy is given in higher doses that are limited by the proximity of normal organs to the radiation dose distribution to improve the likelihood of controlling the tumor in the pancreas while minimizing the risk of radiation injury to these organs. There are two chemotherapy drugs, Capecitabine is an oral drug taken twice per day on the same day that radiation therapy is given and Gemcitabine is an intravenous drug given once per week, during radiation therapy. Everyone in this study will have already received chemotherapy alone first. Everyone in this study will receive radiation therapy and concurrent chemotherapy.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathologically confirmed (histologic or cytologic), locally advanced, adenocarcinoma of the pancreas; patients must have unresectable disease based on institutional standardized criteria of unresectability or medical inoperability.
• Participants with and without regional adenopathy are eligible.
• No distant metastases, based upon the following minimum diagnostic workup:
• History/physical examination, including collection of weight and vital signs, within 28 days prior to study entry;
• Abdominal/pelvic CT scan with IV contrast within 21 days prior to study entry;
• Chest CT scan, or X-ray within 21 days prior to study entry.
• Abdominal/pelvic MR prior to radiation with perfusion and diffusion- weighted sequences and MR and CT sim for radiation planning Pet scan within 21 days prior to study entry, Functional renal study.
• Zubrod performance status 0-1 within 1 week of study entry.
• Age ≥ 18.
• Hematology and cancer antigen (CA) 19-9 / carcinoembryonic antigen (CEA) within 14 days prior to study entry, as follows.
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3;
• Platelets ≥ 100,000 cells/mm^3;
• Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.);
• Serum creatinine ≤ 1.5 mg/dl;
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3 x upper limit of normal (ULN);
• Total bilirubin < 3.0 mg/dL;
• Alkaline phosphatase < 3 x ULN;
• Fasting blood glucose < 160 mg/dl.
• Negative serum pregnancy test (if applicable) within 14 days prior to study entry.
• Ability to swallow oral medications.
• Participants must have had at least 4 months of prior systemic chemotherapy.
• Participants must provide study specific informed consent prior to study entry.
• Women of childbearing potential and male participants who are sexually active must practice adequate contraception.

Exclusion criteria:

• Distant metastatic disease, second malignancy or peritoneal seeding;
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
• Any major surgery within 28 days prior to study entry
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
• Transmural myocardial infarction within 3 months prior to study entry;
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration;
• Uncontrolled malabsorption syndrome significantly affecting gastrointestinal function;
• Any unresolved bowel or bile duct obstruction;
• Major resection of the stomach or small bowel that could affect the absorption of capecitabine
• Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (CDC) definition;
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during the course of the study and for women, for 3 months after the last study drug administration.
• Women who are lactating at the time of registration and who plan to be lactating through 3 months after the last study drug administration.
• Prior allergic reaction to capecitabine or gemcitabine
• Inability to undergo an MR of the abdomen/pelvis
• Participation in another clinical treatment trial while on study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Radiation therapy plus chemotherapy; MR guided dose escalated radiation therapy plus concurrent chemotherapy in unresectable non-metastatic pancreas cancer. Radiation therapy dose escalation to an MR-defined GTV of up to 69.75 Gy at 2.25 Gy per fraction and concurrent Gemcitabine or Capecitabine.

Radiation: Radiation Therapy; Radiation therapy dose escalation to an MR-defined gross tumor volume (GTV) of up to 69.75 Gy at 2.25 Gy per fraction.; Other Names: Dose escalation radiation therapy; Drug: Concurrent chemotherapy (Gemcitabine, Capecitabine); Gemcitabine 400mg/m^2 IV weekly x 6 doses. Capecitabine 825 mg/m^2 by mouth twice daily Monday-Friday on days of radiation use 500 mg tablets.; Other Names: Gemzar; Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	This measure will be the number of subjects alive at one and two years following the end of radiation treatment, up to two years and seven weeks.	1 and 2 years following up to 7 weeks of radiation treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Cancer Antigen 19-9 (CA19-9)	This measure will be the mean serum activity of CA19-9 in units/mL.	Baseline and 1 year
Serum Carcinoembryonic Antigen (CEA)	This measure will be the mean serum concentration of CEA in ng/mL.	Baseline and 1 year
Progression Free Survival	This measure will be the number of subjects achieving a CR or PR or maintaining SD by RECIST 1.1 criteria one and two years following the end of radiation treatment.	1 and 2 years
Radiographic Response	Number of participants treated with the proposed dose escalation achieving CR, PR, or SD measured by RECIST 1.1 criteria from magnetic resonance imaging (MRI), positron emission tomography (PET) or computed tomography (SC) scans.	Baseline and 1 year
Radiation Induced Toxicity	This measure will be the number of subjects experiencing a serious adverse event or grade three or higher non-serious adverse event by CTCAE v4.03 criteria that is definitely, likely, or possibly attributable to the radiation therapy.	3 months post treatment
SMAD 4 Expression	This measure will be the number of participants whose tumor biopsy is positive for the presence of SMAD 4 protein.	Baseline
Efficacy of Dose Escalation	This measure is the change from baseline of gross tumor volume for participants achieving a complete response (CR) or partial response (PR) or maintaining stable disease (SD) by RECIST 1.1 criteria.	Baseline and 1 year

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Investigators: Principal Investigator: Beth Erickson, MD, Froedtert & the Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2015
• Primary Completion (Actual): December 13, 2023
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: August 29, 2013
• First Submitted That Met QC Criteria: October 30, 2013
• First Posted (Estimated): October 31, 2013

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pancreatic cancer
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Gemcitabine; Radiotherapy
• Other Study ID Numbers: 17687

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No