Clinical trial NCT04162665: Pre-operative Adaptive Short Court Radiation Therapy in Gastric Cancer
Official title: Pre-operative Adaptive Short Course Radiation Therapy in Gastric Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Gastric Adenocarcinoma
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Viewray Inc.
First posted: 2019-11-14
Enrollment: 4
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Complete Pathologic Response (pCR - Primary and Nodal) Rate
timeFrame: At the time of surgery (approximately 4.5 months)
Secondary outcomes:
measure: Number of Participants With Local Control
timeFrame: At 1 year post radiation
measure: Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0
timeFrame: From baseline through 12 months after surgery/definitive end of treatment (estimated to be 16.5 months)
measure: Overall Survival
timeFrame: At 1 year post radiation
measure: Number of Participants With Disease-free Survival
timeFrame: At 1 year post radiation
measure: Number of Patients Able to Complete a Full Course of Total Neoadjuvant Chemotherapy
timeFrame: Through completion of neoadjuvant chemotherapy (estimated to be 4.5 months)
Other outcomes:
measure: Average Percentage Difference in Dose to Nearby Organs at Risk (OARs) Due to Variation in OAR Position
timeFrame: Completion of radiation therapy (up to 2 weeks)
measure: Average Percent Difference in Coverage of Planning Target Volume (PTV) by 95% Isodose Line
timeFrame: Completion of radiation therapy (up to 2 weeks)
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Hyun Kim, M.D.
role: PRINCIPAL_INVESTIGATOR
References: