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Magnetic Resonance (MR) Guided, Dose-Escalated Radiation Therapy (RT) + Chemotherapy in Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT01972919
Recruitment Status : Recruiting
First Posted : October 31, 2013
Last Update Posted : November 11, 2021
Sponsor:
Information provided by (Responsible Party):
Beth Erickson, Medical College of Wisconsin

Tracking Information
First Submitted Date  ICMJE August 29, 2013
First Posted Date  ICMJE October 31, 2013
Last Update Posted Date November 11, 2021
Actual Study Start Date  ICMJE December 10, 2015
Estimated Primary Completion Date January 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 23, 2020)
Efficacy of dose escalation [ Time Frame: Baseline and 1 year ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 30, 2013)
To evaluate the efficacy of dose escalation to an MR-defined GTV of up to 69.75 Gy at 2.25 Gy per fraction for unresectable pancreatic cancer. [ Time Frame: One year from the start of treatment ]
To evaluate acute and late (> 3 months post treatment) radiation induced toxicities.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2020)
  • Radiographic response [ Time Frame: Baseline and 1 year ]
    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.
  • Serum Cancer Antigen 19-9 (CA19-9) [ Time Frame: Baseline and 1 year ]
    This measure will be the mean serum activity of CA19-9 in units/mL.
  • Serum Carcinoembryonic Antigen (CEA) [ Time Frame: Baseline and 1 year ]
    This measure will be the mean serum concentration of CEA in ng/mL.
  • Radiation induced toxicity [ Time Frame: 3 months post treatment ]
    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.
  • SMAD 4 expression [ Time Frame: 4 years ]
    This measure will be the number of participants whose tumor biopsy is positive for the presence of SMAD 4 protein.
  • Overall Survival [ Time Frame: 1 and 2 years ]
    This measure will be the number of subjects alive at one and two years following the end of radiation treatment.
  • Progression Free Survival [ Time Frame: 1 and 2 years ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2013)
  • To evaluate radiographic and biochemical response for patients treated with the proposed dose escalation. [ Time Frame: One year from the start of treatment ]
    To evaluate radiographic and biochemical response for patients treated with the proposed dose escalation using pre- and post- treatment MR and PET scanning in addition to routine surveillance CT scans and CEA/ CA 19-9 levels.
  • Radiation induced toxicities [ Time Frame: > 3 months post treatment ]
    To evaluate acute (> 3 months post treatment) and late radiation induced toxicities.
  • SMAD 4 expresssion [ Time Frame: Pre-radiation and post treatment ]
    SMAD 4 expresssion vs pattern of relapse
  • Survival rates [ Time Frame: 7 years ]
    1 & 2 year overall survival, median survival and progression survival rates.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Magnetic Resonance (MR) Guided, Dose-Escalated Radiation Therapy (RT) + Chemotherapy in Pancreatic Cancer
Official Title  ICMJE MR Guided Phase II Radiotherapy Dose Escalation in Unresectable Non-metastatic Pancreatic Cancer
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Unresectable Pancreatic Cancer
Intervention  ICMJE
  • 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 Name: 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
Study Arms  ICMJE 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.
Interventions:
  • Radiation: Radiation Therapy
  • Drug: Concurrent chemotherapy (Gemcitabine, Capecitabine)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 9, 2015)
23
Original Estimated Enrollment  ICMJE
 (submitted: October 30, 2013)
45
Estimated Study Completion Date  ICMJE July 15, 2023
Estimated Primary Completion Date January 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cancer Center Clinical Trials Office 1-800-680-0505 ext 8900 cccto@mcw.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01972919
Other Study ID Numbers  ICMJE 17687
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Beth Erickson, Medical College of Wisconsin
Study Sponsor  ICMJE Medical College of Wisconsin
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Beth Erickson, MD Froedtert & The Medical College of Wisconsin
PRS Account Medical College of Wisconsin
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP