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

NCT ID: NCT03621644

Last Updated: 2022-10-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 133 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-01
• Study Completion Date: 2027-01-31

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.

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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ablative MRIdian SMART

Radiation: Stereotactic MRI-guided On-table Adaptive Radiation Therapy 50 Gy in 5 fractions

Group Type: EXPERIMENTAL

Stereotactic MRI-guided On-table Adaptive Radiation Therapy

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: RADIATION

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Viewray Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Parag J Parikh, MD

Role: PRINCIPAL_INVESTIGATOR

Henry Ford Health System

Percy Lee, MD

Role: PRINCIPAL_INVESTIGATOR

MD Anderson

Daniel Low, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Michael Chuong, MD

Role: PRINCIPAL_INVESTIGATOR

Miami Cancer Institute

Locations

UCLA

Los Angeles, California, United States

University of Miami

Miami, Florida, United States

Miami Cancer Institute

Miami, Florida, United States

Orlando Health

Orlando, Florida, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Henry Ford Health Sciences

Detroit, Michigan, United States

Washington University

St Louis, Missouri, United States

Dartmouth-Hitchcock

Lebanon, New Hampshire, United States

Cornell University

New York, New York, United States

Providence Portland Cancer Center

Portland, Oregon, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Wisconisin

Madison, Wisconsin, United States

Assuta Medical Center

Tel Aviv, , Israel

Countries

United States; Israel

References

Rudra S, Jiang N, Rosenberg SA, Olsen JR, Roach MC, Wan L, Portelance L, Mellon EA, Bruynzeel A, Lagerwaard F, Bassetti MF, Parikh PJ, Lee PP. Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer. Cancer Med. 2019 May;8(5):2123-2132. doi: 10.1002/cam4.2100. Epub 2019 Apr 1.

Reference Type: BACKGROUND

PMID: 30932367 (View on PubMed)

Parikh PJ, Lee P, Low DA, Kim J, Mittauer KE, Bassetti MF, Glide-Hurst CK, Raldow AC, Yang Y, Portelance L, Padgett KR, Zaki B, Zhang R, Kim H, Henke LE, Price AT, Mancias JD, Williams CL, Ng J, Pennell R, Pfeffer MR, Levin D, Mueller AC, Mooney KE, Kelly P, Shah AP, Boldrini L, Placidi L, Fuss M, Chuong MD. A Multi-Institutional Phase 2 Trial of Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided On-Table Adaptive Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer. Int J Radiat Oncol Biol Phys. 2023 Nov 15;117(4):799-808. doi: 10.1016/j.ijrobp.2023.05.023. Epub 2023 May 19.

Reference Type: DERIVED

PMID: 37210048 (View on PubMed)

Related Links

https://vimeo.com/235284105

Parag Parikh, MD: Improving Pancreatic Cancer Survival by using MR Guided Adaptive Radiation

Other Identifiers

VR C2T2 - SMART - LAPC/BRPC 1

Identifier Type: -

Identifier Source: org_study_id