Pre-operative Adaptive Short Court Radiation Therapy in Gastric Cancer

Pre-operative Adaptive Short Course Radiation Therapy in Gastric Cancer

Gastric cancer is a global health issue as the world's fifth most common malignancy and third leading cause of cancer mortality, respectively. Preoperative radiation therapy may improve overall survival (OS) but is seldom used. There is precedent for preoperative chemoradiation, as it is the standard of care for esophageal and gastroesophageal junction tumors. However, reluctance of physicians to prescribe preoperative radiation therapy in gastric cancer may be due to the large treatment fields necessary to account for stomach motion. Adaptive radiation therapy may permit decreased field sizes and more accurate dose delivery. In traditional CT based radiation delivery the same radiation plan is delivered each day without assessment of inter-fraction or intra-fraction motion. Adaptive radiation therapy permits the physician to contour the unique anatomy daily to generate a new plan to account for day to day organ motion. Real-time MR imaging is also used during the treatment so that radiation is only delivered when the tumor is within the pre-specified target area. Thus, adaptive radiation therapy may overcome traditional barriers of radiation delivery in gastric cancer and improve oncologic outcomes.

Study Overview

• Status: Recruiting
• Conditions: Gastric Adenocarcinoma
• Intervention / Treatment: Drug: Standard of care chemotherapy regimen; Radiation: Adaptive short course radiation therapy

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hyun Kim, M.D.; Phone Number: 314-362-8502; Email: kim.hyun@wustl.edu

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Withdrawn
    • Seoul National University Hospital
• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Katrina Pedersen, M.D.
      • Sub-Investigator: Kian-Huat Lim, M.D., Ph.D.
      • Sub-Investigator: Patrick Grierson, M.D.
      • Sub-Investigator: Natasha Leigh, M.D.
      • Sub-Investigator: Pamela Samson, M.D.
      • Sub-Investigator: William Hawkins, M.D.
      • Sub-Investigator: Dominic Sanford, M.D.
      • Sub-Investigator: Rama Suresh, M.D.
      • Sub-Investigator: Benjamin Tan, M.D.
      • Contact: Hyun Kim, M.D.; Phone Number: 314-362-8502; Email: kim.hyun@wustl.edu
      • Principal Investigator: Hyun Kim, M.D.
      • Sub-Investigator: Ryan Fields, M.D.
      • Sub-Investigator: Carl DeSelm, M.D., Ph.D.
      • Sub-Investigator: Roheena Panni, M.D., Ph.D.
      • Sub-Investigator: Allen Mo, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Newly diagnosed histologically or cytologically gastric adenocarcinoma. (Siewert III acceptable: the bulk of tumor should be in stomach; gastric tumors with extension to the gastroesophageal junction are permitted.) Patients with T1-3N0-2 are eligible. Patients with N3, or T4 disease are not eligible.
• Known T-stage defined by EUS. Must have had CT of the chest/abdomen/pelvis with contrast.
• Medically eligible to receive standard of care chemotherapy.
• At least 19 years of age
• ECOG performance status ≤ 2

Normal bone marrow and organ function as defined below:

• Absolute neutrophil count ≥ 1,500 cells/mm3
• Platelets ≥ 100,000 cells/mm3

• Creatinine clearance > 50 mL/min

  • The effects of the various chemotherapy agents used in this study on the developing human fetus are unknown. For this reason, 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and one month after completion of the study
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Prior surgery, radiation, or chemotherapy for gastric or esophageal cancer.
• Prior surgery to the esophagus or stomach that would alter the radiation treatment field or stomach motion.
• Siewert I-II GE junction tumor
• Any active malignancy within 2 years of enrollment that may alter the course of gastric cancer. (Apparently cured localized malignancy or advanced, but indolent malignancy with significantly more favorable prognosis are allowed).
• Currently receiving any other investigational agents.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to chemotherapeutic agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, diabetes, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia that are considered clinically significant as determined by the treating physician.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
• Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended. Recommend exclusion of specific ART agents based on predicted drug-drug interactions (i.e. for sensitive CYP3A4 substrates, concurrent strong CYP3A4 inhibitors (ritonavir and cobicistat) or inducers (efavirenz) should be contraindicated).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pre-operative adaptive short course radiation therapy; Consenting and eligible patients will receive adaptive short course radiation therapy (SCRT) (25 Gy at in 5 fractions), followed by standard of care total neoadjuvant chemotherapy followed by standard of care gastrectomy or esophagogastrectomy. The recommended SOC chemotherapy options are CAPOX, FOLFOX, or FLOT, but any SOC total neoadjuvant chemotherapy may be given at the discretion of the treating medical oncologist after consultation with the study chair. Patients who are not able to complete their full total neoadjuvant therapy regimen prior to surgery may complete chemotherapy postoperatively at the discretion of the treating physician.

Drug: Standard of care chemotherapy regimen; The recommendations are CAPOX, FOLFOX, or FLT.; Radiation: Adaptive short course radiation therapy; Radiation must be livered with adaptive planning and MR gating or CBCT breath hold treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete pathologic response (pCR - primary and nodal) rate	pCR: no pathological signs of cancer	At the time of surgery (approximately 4.5 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of grade 3 or greater toxicity as defined by CTCAE version 5.0		From baseline through 12 months after surgery/definitive end of treatment (estimated to be 16.5 months)
Proportion of patients able to complete a full course of total neoadjuvant chemotherapy		Through completion of neoadjuvant chemotherapy (estimated to be 4.5 months)
Local control rate	Local control from the time of gastrectomy	At 1 year post radiation
Overall survival	-Overall survival from registration on trial	At 1 year post radiation
Disease-free survival	-Disease free means no locoregional and distant recurrence	At 1 year post radiation

Other Outcome Measures

Outcome Measure	Time Frame
Average percentage difference in dose to nearby organs at risk (OARs) due to variation in OAR position	Completion of radiation therapy (up to 2 weeks)
Average percent difference in coverage of planning target volume (PTV) by 95% isodose line	Completion of radiation therapy (up to 2 weeks)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Viewray Inc.
• Investigators: Principal Investigator: Hyun Kim, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2020
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: November 11, 2019
• First Submitted That Met QC Criteria: November 11, 2019
• First Posted (Actual): November 14, 2019

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Adenocarcinoma
• Other Study ID Numbers: 201911059

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in the journal publication, after deidentification (text, tables, figures, and appendices)
• IPD Sharing Time Frame: Beginning 9 months and ending ending 36 months following publication
• IPD Sharing Access Criteria: Investigators whose proposed use of the data has been approved by the Washington University School of Medicine IRB. The data will be available for individual participant data meta-analysis. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• 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