Gastric Adenocarcinoma
Conditions
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.
Interventions
RADIATIONAdaptive short course radiation therapy
Radiation must be livered with adaptive planning and MR gating or CBCT breath hold treatment.
The recommendations are CAPOX, FOLFOX, or FLT.
Sponsors
Viewray Inc.
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Pathologic Response (pCR - Primary and Nodal) Rate | At the time of surgery (approximately 4.5 months) | pCR: no pathological signs of cancer |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Local Control | At 1 year post radiation | Local control calculated from start of radiation. |
| Number 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) | — |
| Overall Survival | At 1 year post radiation | -Overall survival from start of radiation. |
| Number of Participants With Disease-free Survival | At 1 year post radiation | -Disease free means no locoregional and distant recurrence |
| Number of Patients Able to Complete a Full Course of Total Neoadjuvant Chemotherapy | Through completion of neoadjuvant chemotherapy (estimated to be 4.5 months) | — |
Other
| 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Pre-operative Adaptive Short Course Radiation Therapy |
|---|---|
| Age, Continuous | 73.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 3 / 4 |
Outcome results
Primary
Complete Pathologic Response (pCR - Primary and Nodal) Rate
pCR: no pathological signs of cancer
Time frame: At the time of surgery (approximately 4.5 months)
Population: 2 participants did not have surgery due to poor functional status and were not evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pre-operative Adaptive Short Course Radiation Therapy | Complete Pathologic Response (pCR - Primary and Nodal) Rate | 2 Participants |
Secondary
Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0
Time frame: From baseline through 12 months after surgery/definitive end of treatment (estimated to be 16.5 months)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Febrile neutropenia | 2 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Anemia | 2 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | GI bleed | 1 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Gastric obstruction | 1 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Failure to thrive | 2 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Cholecystitis | 1 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Lung infection | 1 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Urinary tract infection | 1 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Blood bilirubin increased | 1 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Lymphocyte count decreased | 2 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Neutrophil count decreased | 1 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | White blood cell decreased | 2 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Dehydration | 1 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Hypoalbuminemia | 2 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Syncope | 1 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Delirium | 1 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Pre-renal azotemia | 1 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Acute kidney injury | 1 Participants |
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Grade 3 or Greater Toxicity as Defined by CTCAE Version 5.0 | Percutaneous endoscopic gastromy tube clogging | 1 Participants |
Secondary
Number of Participants With Disease-free Survival
-Disease free means no locoregional and distant recurrence
Time frame: At 1 year post radiation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Participants With Disease-free Survival | 4 Participants |
Secondary
Number of Participants With Local Control
Local control calculated from start of radiation.
Time frame: At 1 year post radiation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Participants With Local Control | 4 Participants |
Secondary
Number of Patients Able to Complete a Full Course of Total Neoadjuvant Chemotherapy
Time frame: Through completion of neoadjuvant chemotherapy (estimated to be 4.5 months)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pre-operative Adaptive Short Course Radiation Therapy | Number of Patients Able to Complete a Full Course of Total Neoadjuvant Chemotherapy | 3 Participants |
Secondary
Overall Survival
-Overall survival from start of radiation.
Time frame: At 1 year post radiation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pre-operative Adaptive Short Course Radiation Therapy | Overall Survival | 4 Participants |
Other Pre-specified
Average Percentage Difference in Dose to Nearby Organs at Risk (OARs) Due to Variation in OAR Position
Time frame: Completion of radiation therapy (up to 2 weeks)
Other Pre-specified
Average Percent Difference in Coverage of Planning Target Volume (PTV) by 95% Isodose Line
Time frame: Completion of radiation therapy (up to 2 weeks)