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
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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||133 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
- 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.
- 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
- Overall survival [ Time Frame: 2 years ]Percentage of patients dying from any cause
- Distant progression-free survival [ Time Frame: 6 months ]Percentage of patients whose pancreatic cancer does not progress
- 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
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
|Contact: Jill Farenbaughemail@example.com|
|Contact: Martin Fuss, MD||(650) firstname.lastname@example.org|
|United States, Florida|
|University of Miami||Recruiting|
|Miami, Florida, United States, 33136|
|Contact: Lorraine Portelance, MD email@example.com|
|United States, Michigan|
|Henry Ford Health Sciences||Recruiting|
|Detroit, Michigan, United States, 48202|
|Contact: Parag Parikh, MD 313-207-5746 firstname.lastname@example.org|
|United States, Missouri|
|Saint Louis, Missouri, United States, 63108|
|Contact: Hyun Kim, MD email@example.com|
|United States, Wisconsin|
|University of Wisconisin||Recruiting|
|Madison, Wisconsin, United States, 53792|
|Contact: Michael Bassetti, MD firstname.lastname@example.org|
|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|