Adaptive Radiation Therapy before Surgery for the Treatment of Stage I-III Gastric Cancer
This trial studies how well adaptive radiation therapy works before surgery for the treatment of stages I-III gastric cancer. Radiation therapy uses high-energy magnetic fields and radio waves to kill cancer cells and shrink tumors. Adaptive radiation therapy uses a machine (called the Viewray System or Ethos System) that contains both the device that delivers the radiation and an imaging scanner. This may help the doctors to adjust or re-plan treatment day by day.
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 endoscopic ultrasonography (EUS). Must have had CT of the chest/abdomen/pelvis with intravenous (IV) contrast
- Medically eligible to receive standard of care (SOC) chemotherapy
- At least 19 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Absolute neutrophil count >= 1,500 cells/mm^3
- Platelets >= 100,000 cells/mm^3
- 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 Institutional Review Board (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 gastroesophageal (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)
- 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 human immunodeficiency virus (HIV) are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective assisted reproductive technology (ART) according to Department of Health and Human Services (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 sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04162665.
PRIMARY OBJECTIVE:
I. To quantify the pathologic complete response (pCR) rate in gastric cancer patients treated with preoperative radiation followed by total neoadjuvant chemotherapy.
SECONDARY OBJECTIVES:
I. To quantify the proportion of patients able to complete a full course of total neoadjuvant chemotherapy.
II. To quantify the local control rate of gastric cancer patients treated with preoperative radiation followed by chemotherapy.
III. To quantify the toxicity of gastric patients treated with preoperative radiation followed by chemotherapy.
IV. To quantify the overall survival in gastric patients treated with preoperative radiation followed by chemotherapy.
V. To quantify the disease free survival in gastric patients treated with preoperative radiation followed by chemotherapy.
EXPLORATORY OBJECTIVES:
I. To quantify the deviation in dose to the tumor due to variation in stomach position.
II. To quantify the deviation in dose to organs at risk (OARs) due to variation in OAR position.
III. To determine the distribution of The Cancer Genome Atlas (TCGA) molecular subtypes in Korean and Western gastric adenocarcinoma after radiation and chemotherapy.
IV. To identify differentially expressed post-treatment biomarkers.
V. To correlate circulating tumor DNA (ctDNA) levels with clinical outcomes.
OUTLINE:
Patients undergo adaptive radiation therapy once daily (QD) for a total of 5 fractions over 5-12 days. Beginning 2-4 weeks after radiation therapy, patients also receive standard of care neoadjuvant chemotherapy regimen at the discretion of treating medical oncologist. Patients then undergo gastrectomy or esophagogastrectomy. Additionally, patients undergo computed tomography (CT) and blood sample collection throughout the trial, as well as magnetic resonance imaging (MRI) and an optional positron emission tomography (PET)/CT at baseline.
After completion of study treatment, patients are followed up at 3, 6, and 12 months.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorHyun Kim
- Primary ID201911059
- Secondary IDsNCI-2019-08527
- ClinicalTrials.gov IDNCT04162665