Clinical trial NCT05387681: Preoperative Short Course Radiotherapy With Envafolimab, Endostatin and SOX Regimen in Locally Advanced Gastric
Official title: An Exploratory Clinical Study of Short-course Radiotherapy Combined With Envafolimab, Endostatin and SOX Regimen for Neoadjuvant Treatment of Resectable Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Gastric/Gastroesophageal Junction Adenocarcinoma
Radiotherapy
Immunotherapy
Keywords: neoadjuvant，gastric
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
First posted: 2022-05-24
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm, exploratory clinical study to evaluate the efficacy and safety of Preoperative short course radiotherapy with Envafolimab, Endostatin and SOX regimen in resectable locally advanced gastric/gastroesophageal junction adenocarcinoma.

Detailed description: All eligible subjects will receive 5\*5Gy (25Gy/5F) fractionated radiotherapy, rest for 1 week, 3 cycles of Envafolimab, Endostatin and SOX regimen, and radical surgery 2 to 4 weeks after completion of the last neoadjuvant therapy, according to the study plan. Each patient will be followed up 12 months after initiation of treatment in the study. Whether the subjects need adjuvant therapy after surgery and the adjuvant treatment plan are determined by the investigator. All subjects were required to complete the study follow-up plan after surgery.

Eligibility criteria: Inclusion Criteria:

1. Signed written informed consent before enrollment; 2.18 years old ≤75 years old, male or female; 3. Initially diagnosed locally advanced gastric/gastroesophageal junction adenocarcinoma confirmed by tissue or pathology; 4. Without systemic treatment; 5. Patients diagnosed as CT2-4an + M0 according to endoscopic ultrasonography or enhanced CT/MRI scan cTNM were assessed by researchers as suitable for neoadjuvant therapy + radical surgery. AJCC/UICC Version 8 was used for TNM pathological staging (pTNM).

6.ECOG PS score: 0 \~ 1; 7. The expected survival time is more than 6 months; 8. The function of vital organs meets the following requirements (excluding any blood components and cell growth factors within 14 days) :

1. Blood routine:

   Neutrophils ≥1.5×109/L Platelet count ≥100×109/L Hemoglobin ≥ 90g/L;
2. Liver and kidney function:

Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal value (ULN) or creatinine clearance ≥50 mL /min (Cockcroft-Gault formula); Total bilirubin (TBIL) ≤ 1.5 times normal upper limit (ULN); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels ≤ 2.5 times the upper limit of normal value (ULN) (≤5ULN if abnormal liver function is due to liver metastasis); Urine protein \& lt; 2 +; If urine protein ≥2+, 24-hour urine protein quantification must be ≤1g; 9. Normal coagulation function, no active bleeding and thrombotic diseases

1. International standardized ratio INR≤1.5×ULN;
2. Partial thrombin time APTT≤1.5×ULN;
3. Prothrombin time PT≤1.5×ULN; 10. Women of non-surgical sterilization or childbearing age are required to use a medically approved contraceptive method (such as an intrauterine device, birth control pill or condom) during the study period and for three months after the study period; The serum or urine HCG test of female patients of reproductive age who were not undergoing surgical sterilization must be negative within 7 days prior to study enrollment. And must be non lactation period; Male patients of non-surgical sterilization or reproductive age are required to consent with their spouse to use a medically approved contraceptive method during the study treatment period and for 3 months after the study treatment period 11. The subjects voluntarily participated in the study with good compliance and follow-up for safety and survival.

Exclusion Criteria:

1. The subject has previous or co-existing malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
2. Previous treatment with other PD-1/PD-L1 inhibitors could not be included; Subject is known to have a prior allergy to large protein preparations, or is known to be allergic to the drug ingredient used;
3. The subjects exist any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, the pituitary gland inflammation, vasculitis, nephritis, thyroid function hyperfunction, thyroid function is reduced, always had thyroid surgery must be incorporated into; Subjects with vitiligo or asthma in complete remission during childhood without any intervention as adults could be included; Subjects with asthma requiring medical intervention with bronchodilators were excluded);
4. Subject is receiving immunosuppressant, or systemic, or absorbable local hormone therapy for immunosuppression purposes (dose \&gt; 10mg/ day of prednisone or other equivalent hormone) and continued to use within 2 weeks prior to enrollment;
5. Clinical ascites or pleural effusion requiring therapeutic puncture or drainage;
6. Patients with cardiac clinical symptoms or diseases that are not well controlled, such as :(1) nyha class 2 or more heart failure (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant ventricular or ventricular arrhythmias requiring treatment or intervention;
7. Within 14 days before the first administration of the study drug, Chinese herbal medicines or proprietary Chinese medicines approved by the National Medical Products Administration of China (NMPA) with antitumor activity, regardless of cancer type;
8. Subject has active infection or unexplained fever during screening but prior to initial administration \& GT; 38.5 degrees (the investigator judged that the fever caused by the tumor could be included in the study);
9. Patients with past or present objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radioactive pneumonia, drug-associated pneumonia, known active tuberculosis, severely impaired lung function, etc.;
10. Subjects with congenital or acquired immune deficiency (such as HIV infection, HIV 1/2 antibody positive);
11. Patients with acute or chronic active Hepatitis B (HBsAg or core antibody.HBcAb) should be tested for Hepatitis B virus (HBV)DNA, such as HBV DNA copy number ≤2×103 copy number/mL or ≤200 IU/ mL or lower than the detection limit can be included. HBsAg (+) subjects should receive anti-HBV therapy throughout study drug therapy to avoid viral activation. Subjects who are resistant to HBc(+), HBsAg(-), anti-HBS (-), and HBV viral load (-) do not need prophylactic anti-HBV therapy, but should be closely monitored for virus reactivation;
12. Acute or chronic active Hepatitis C Virus (HCV), that is, HCV antibody positive and HCV RNA levels above the detection limit;
13. Received live vaccine less than 4 weeks prior to study administration or possibly during the study period;
14. The subject has a known history of psychotropic drug abuse, alcoholism or drug abuse;
15. Known Her2 positive;
16. Prone to stomach bleeding; Patients with any evidence or history of bleeding; Patients with any bleeding or bleeding event ≥CTCAE grade 3 within 4 weeks prior to grouping had unhealed wounds, ulcers or fractures;
17. Researchers think that should be left out in this study, the researchers determine, for example, the subjects have other factors that may result in this study were forced to midway termination, such as, other serious disease (including mental illness) need to merge treatment, there are serious abnormal laboratory examination, accompanied by factors such as family or society, will affect the safety of the subjects, or information and the collection of the sample.

Primary outcomes:
measure: pathological complete response (pCR)
timeFrame: one year
Secondary outcomes:
measure: R0 resection rates
timeFrame: one year
measure: pathological partial response(MPR)
timeFrame: one year
Other outcomes:
Locations:
Study officials:
affiliation: Cancer Center, Union Hospital, Tongji Medical College
name: Tao Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li J, Deng Y, Zhang W, Zhou AP, Guo W, Yang J, Yuan Y, Zhu L, Qin S, Xiang S, Lu H, Gong J, Xu T, Liu D, Shen L. Subcutaneous envafolimab monotherapy in patients with advanced defective mismatch repair/microsatellite instability high solid tumors. J Hematol Oncol. 2021 Jun 21;14(1):95. doi: 10.1186/s13045-021-01095-1.