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

Sponsor

Viewray Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03621644

Collaborator

(none)

133

Enrollment

Locations

Anticipated Duration (Months)

10.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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 3 and 12 months post-treatment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

133 participants

Allocation:

N/A

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 :

Jan 1, 2019

Anticipated Primary Completion Date :

May 1, 2022

Anticipated Study Completion Date :

Jan 1, 2026

Outcome Measures

Primary Outcome Measures

Gastrointestinal toxicity assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5 [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

Overall survival [2 years]
Percentage of patients dying from any cause
Distant progression-free survival [6 months]
Percentage of patients whose pancreatic cancer does not progress
Patient-reported quality of life (QOL) [3 and 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
Greater than or equal to 3 months of systemic chemotherapy
At least 18 years of age.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Normal bone marrow and organ function as defined below:
Absolute neutrophil count ≥ 500/mcL (microliters)
Platelets ≥ 50,000/mcL
Hemoglobin ≥ 8.0 g/dL (deciliters)
Total bilirubin ≤ 1.5 x IULN
Aspartate Aminotransferase AST(SGOT) / Alanine Aminotransferase ALT(SGPT) ≤ 3.0 x Institutional Upper Limit of Normal (IULN)
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.
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:

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
Carbohydrate antigen (CA19.9) > 500 U/ml.
Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
Currently receiving any other investigational agents.
Major surgery within 4 weeks prior to first day of treatment.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
Medical/psychological contraindication to magnetic resonance imaging (MRI).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA	Los Angeles	California	United States	90095
2	University of Miami	Miami	Florida	United States	33136
3	Miami Cancer Institute	Miami	Florida	United States	33176
4	Orlando Health	Orlando	Florida	United States	32806
5	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
6	Henry Ford Health Sciences	Detroit	Michigan	United States	48202
7	Washington University	Saint Louis	Missouri	United States	63108
8	Dartmouth-Hitchcock	Lebanon	New Hampshire	United States	03756
9	Cornell University	New York	New York	United States	10065
10	Providence Portland Cancer Center	Portland	Oregon	United States	97213
11	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
12	University of Wisconisin	Madison	Wisconsin	United States	53792
13	Assuta Medical Center	Tel Aviv		Israel