Overview
This phase II trial studies how well radiation therapy works for the treatment of gastrointestinal cancer that are spreading to other places in the body (metastatic). Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. This trial is being done to determine if giving radiation therapy to patients who are being treated with immunotherapy and whose cancers are progressing (getting worse) can slow or stop the growth of their cancers. It may also help researchers determine if giving radiation therapy to one tumor can stimulate the immune system to attack other tumors in the body that are not targeted by the radiation therapy.
Description
PRIMARY OBJECTIVE:
I. To determine whether radiation therapy can convert overall response rates from progressive disease to stable or responsive disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1.
SECONDARY OBJECTIVES:
I. To define overall response rate by immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST) criteria.
II. To determine time to progression. III. To determine overall survival. IV. To determine local control in radiated lesion(s). V. To characterize the effect of distant radiation on unirradiated target lesions.
VI. To describe the incidence of new metastatic lesions. VII. To determine treatment safety by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0.
VIII. To describe time to new systemic therapy.
EXPLORATORY OBJECTIVES:
I. To define radiation-induced effects on circulating immune cells. II. To describe remodeling of the circulating T cell repertoire by deep sequencing of variable, diversity and joining (VDJ) regions of T cell receptors (TCRs).
III. To describe changes in circulating tumor deoxyribonucleic acid (DNA) (ctDNA).
- OUTLINE
Patients undergo radiation therapy for a total of 5 treatments over 5-9 calendar days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 14 day, 6 months, and then up to 36 months.
Eligibility
Inclusion Criteria:
- Agree to follow the trial treatment regimen, visit schedule, laboratory test, and other requirements of the protocol, and voluntarily enroll in the study and sign the written informed consent.
- Age ≥ 18 years at the time of signing the informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
- The expected survival time is at least 12 weeks.
- According to the evaluation of RECIST 1.1 standard, the subjects enrolled have at least one measurable lesion.
- Patients with histologically confirmed unresectable locally advanced or metastatic gastric/gastroesophageal junction (G/GEJ) adenocarcinoma.
- There is adequate organ and bone marrow function,Conforms to laboratory test results.
- Males with fertility and females of childbearing age are willing to take effective contraceptive measures From the signing of the informed consent form to within 6 months after the last administration of the trial drug (including abstinence, intrauterine device, various hormonal contraception, correct use of contraception Sets，etc）; Women of childbearing age include pre-menopausal women and women within 2 years after menopause. Women of childbearing age must have a negative pregnancy test within 7 days before the first trial drug is administered.
Exclusion Criteria:
- Participation in clinical studies of antineoplastic agents within 4 weeks before the first use of study drug,or is expected to receive any other form of systemic anti-tumor therapy outside the protocol during the study.
- Use of immunomodulatory drugs within 2 weeks before the first use of study drug,Including but not limited to thymopeptide, interleukins, interferon, etc.
- Patients with active, or who have had and have the possibility of recurrence of autoimmune diseases.
- Patients with clinically uncontrollable pleural effusion, pericardial effusion, ascites, and those requiring repeated drainage or medical intervention.
- The patient has a Medical history of immunodeficiency, including HIV antibody positive.
- Active hepatitis B or active hepatitis C.
- Women during pregnancy or lactation.
- The investigator believes that the subject has other conditions that may affect compliance or are not suitable for participating in this study.
