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Stereotactic MRI-guided On-table Adaptive Radiation Therapy (SMART) for Locally Advanced Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT03621644
Recruitment Status : Recruiting
First Posted : August 8, 2018
Last Update Posted : July 11, 2019
Sponsor:
Information provided by (Responsible Party):
Viewray Inc.

Brief Summary:

High-dose magnetic resonance imaging (MRI) guided hypofractionated radiation therapy delivered using daily adaptive dose planning has been shown in a retrospective study to result in improved overall survival, relative to patients receiving lower radiation doses, in patients with locally advanced pancreatic cancer, without increasing the rate of serious gastrointestinal toxicity.

The goal of the proposed trial is to investigative in a controlled, prospective manner the robustness of this outcome, and to track quality of life over a 5-year trial period.


Condition or disease Intervention/treatment Phase
Pancreatic Cancer Radiation: Stereotactic MRI-guided On-table Adaptive Radiation Therapy Phase 2

Detailed Description:

Prior stereotactic body radiotherapy (SBRT) experiences for treatment of locally advanced pancreatic cancer entailed either single-fraction or multi-fraction approaches delivering 33 Gray (Gy) in 5 fractions. Excellent tolerance and tumor control has been demonstrated, but median survival remained approximately 14 months. This highlights the strengths and limitations of SBRT to current radiation doses for pancreatic cancer. A prior Washington University institutional study and retrospective review has shown the safety of delivering 67.5 Gy in 15 fractions for inoperable pancreatic cancer using a strict 'isotoxicity' approach of limiting the gastrointestinal (GI) organs at risk (stomach, duodenum, small bowel and large bowel) to 45 Gy to 0.5 cm3 or less. This regimen resulted in no grade 3 or higher GI toxicities, and only one death in the 19 patients with a median follow-up of 15 months. This is significantly improved from prior experiences, where approximately 15 months represents the median survival for most studies of inoperable pancreatic cancer.

A recent retrospective analysis of 42 locally advanced pancreatic cancer patients treated by magnetic resonance imaging (MRI) guided radiation therapy at four institutions (University of California, Los Angeles, University of Wisconsin, Vrije Universiteit Medical Center (VUmc), Amsterdam, and Washington University, St. Louis) demonstrated that high-dose stereotactic body radiotherapy (SBRT) or hypofractionated radiation therapy delivered using daily ADAPTIVE dose planning on an MRI-guided radiotherapy system (MRIdian, ViewRay Inc.) has the potential to further improve overall survival. A control group of 19 patients treated to more conventional radiation doses without frequent dose adaptation showed a median survival of 14.8 months, while patients treated to high radiation doses (n=23, maximum biologically equivalent dose at alpha/beta = 10 Gy, or BED10 of > 90 Gy) under daily or almost daily adaptive re-planning had an estimated median survival of 27.8 months (p=0.005). Interestingly, increased radiation dose delivery using daily dose adaptation was correlated with less grade 3 toxicity (0% in the high dose group vs 15.8% in patients treated to lower radiation doses without dose adaptation).

The compelling data of this retrospective study prompted the development of this current prospective clinical trial designed to assess the primary objective of grade 3 or greater GI toxicity at 90 days for patients with borderline resectable or inoperable locally advanced pancreatic cancer treated with MRI-guided on-table adaptive radiation therapy and soft tissue tracking with radiation beam gating to 50 Gy in 5 fractions. Secondary objectives include assessment of (1) overall survival at 2 years, (2) distant progression free survival at 6 months, and (3) changes in patient-reported quality of life (QOL) from pre-treatment to 12 months post-treatment.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 133 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Phase II Study of Stereotactic Magnetic Resonance Imaging (MRI) Guided On-table Adaptive Radiation Therapy (SMART) for Patients With Borderline or Inoperable Locally Advanced Pancreatic Cancer
Actual Study Start Date : January 1, 2019
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : January 2026

Resource links provided by the National Library of Medicine



Intervention Details:
  • Radiation: Stereotactic MRI-guided On-table Adaptive Radiation Therapy
    Radiation therapy will be delivered with an integrated magnetic resonance imaging (MRI)-guided radiotherapy delivery system (ViewRay MRIdian or MRIdian Linac). The prescribed dose will be 50 Gray (Gy) in 5 fractions. Stereotactic body radiotherapy (SBRT) fractions will be delivered at least twice per week, and with at least 18 hours between fractions. Each participant will be aligned in the treatment system with MRI image-guidance. On-table adaptive re-planning will be used when clinically indicated. In all patients, real-time MRI imaging will be used throughout treatment delivery to monitor the target location and control the radiation beam as necessary.


Primary Outcome Measures :
  1. Gastrointestinal toxicity assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5 [ Time Frame: 90 days ]
    Grade 3 or higher gastrointestinal toxicity assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5 within 90 days of completion of radiation therapy


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 2 years ]
    Percentage of patients dying from any cause

  2. Distant progression-free survival [ Time Frame: 6 months ]
    Percentage of patients whose pancreatic cancer does not progress

  3. Patient-reported quality of life (QOL) [ Time Frame: 12 months ]

    Patient-reported assessments using the National Comprehensive Cancer Network (NCCN) Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index, 18-item Hepatobiliary Cancer Subscale (FHSI-18) (NCCN FACT FHSI-18)

    The FACT FHSI-18 is an 18-item scale, each item answered by patients on a scale of 0 ("not at all") to 4 ("very much"). The Total Scale breaks down into 4 subscales as indicated below:

    Total Scale Range: 0-72 (where 72 is good; high scores on each subscale are good)

    Disease-Related Symptoms Subscale-Physical (DRS-P): 12 items, score range 0-48

    Disease-Related Symptoms Subscale - Emotional (DRS-E): 2 items, score range 0-8

    Treatment Side Effects Subscale (TSE): 1 item, score range 0-4

    Function and Well-Being Subscale (FWB): 3 items, score range 0-12

    To view all the FHSI-18 items, see http://www.facit.org/facitorg/questionnaires




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed locally advanced adenocarcinoma of the pancreas that is considered unresectable or borderline resectable on institutional standardized criteria of unresectability or medical inoperability. Patients with and without regional adenopathy are eligible as long as lymph nodes are adjacent to primary tumor.
  2. Greater than or equal to 3 months of systemic chemotherapy
  3. At least 18 years of age.
  4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  5. Normal bone marrow and organ function as defined below:

    1. Absolute neutrophil count ≥ 500/mcL (microliters)
    2. Platelets ≥ 50,000/mcL
    3. Hemoglobin ≥ 8.0 g/dL (deciliters)
    4. Total bilirubin ≤ 1.5 x IULN
    5. Aspartate Aminotransferase AST(SGOT) / Alanine Aminotransferase ALT(SGPT) ≤ 3.0 x Institutional Upper Limit of Normal (IULN)
  6. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  7. Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

  1. Distant metastatic disease as assessed by staging positron emission tomography / computed tomography (PET/CT) or CT of the chest and abdomen within 6 weeks of starting radiation therapy
  2. Carbohydrate antigen (CA19.9) > 500 U/ml.
  3. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
  4. Currently receiving any other investigational agents.
  5. Major surgery within 4 weeks prior to first day of treatment.
  6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
  7. Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
  8. Medical/psychological contraindication to magnetic resonance imaging (MRI).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03621644


Contacts
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Contact: Jill Farenbaugh 612-412-7389 jfarenbaugh@viewray.com
Contact: Martin Fuss, MD (650) 252-2067 mfuss@viewray.com

Locations
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United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Lorraine Portelance, MD       lportelance@med.miami.edu   
United States, Michigan
Henry Ford Health Sciences Recruiting
Detroit, Michigan, United States, 48202
Contact: Parag Parikh, MD    313-207-5746    pparikh2@hfhs.org   
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63108
Contact: Hyun Kim, MD       kim.hyun@wustl.edu   
United States, Wisconsin
University of Wisconisin Recruiting
Madison, Wisconsin, United States, 53792
Contact: Michael Bassetti, MD       bassetti@humonc.wisc.edu   
Sponsors and Collaborators
Viewray Inc.
Investigators
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Principal Investigator: Parag J Parikh, MD Henry Ford Health System
Principal Investigator: Percy Lee, MD University of California, Los Angeles
Principal Investigator: Daniel Low, PhD University of California, Los Angeles

Additional Information:
Publications of Results:
S. Rudra, N. Jiang, S.A. Rosenberg, J.R. Olsen, P.J. Parikh, M.F. Bassetti, P. Lee. High Dose Adaptive MRI Guided Radiation Therapy Improves Overall Survival of Inoperable Pancreatic Cancer IJROBP October 1, 2017Volume 99, Issue 2, Supplement, Page E184

Other Publications:
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Responsible Party: Viewray Inc.
ClinicalTrials.gov Identifier: NCT03621644     History of Changes
Other Study ID Numbers: VR C2T2 - SMART - LAPC/BRPC 1
First Posted: August 8, 2018    Key Record Dates
Last Update Posted: July 11, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Viewray Inc.:
Pancreatic Cancer
Radiation Therapy
SBRT
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases