This study aims to evaluate the efficacy and safety of Sintilimab plus CAPOX in the
conversion therapy for patients with unresectable locally advanced or limited metastatic
adenocarcinoma of the stomach or esophagogastric junction
In a variety of solid tumors such as colorectal cancer, it has been confirmed that some
selected advanced patients still have a chance to cure through multidisciplinary treatment.
Because of the poor biological behavior of gastric cancer, few people with advanced gastric
cancer can benefit from local treatment, and there are fewer related studies. However,
retrospective and small sample size prospective phase II clinical studies have also shown
that unresectable locally advanced and some selected limited distant metastatic gastric and
gastric junction adenocarcinoma patients may also achieve long-term survival through
multimodal treatment strategies. The triple drug regimens were often used as conversion
regimens in previous studies. Although the efficiency was improved, the R0 resection rate was
only about 60%, the disease-free survival was about 10 months, and the toxicity was high. In
order to improve the survival of these patients, more effective and less toxic treatment
regimens are urgently needed. Objective response rate was 76.5% with anti-PD-1 antibody
nivolumab plus CapeOX. The investigators predict that this regimen will achieve good results
in the conversion treatment of advanced gastric cancer. The investigators intend to carry out
this study to evaluate the efficacy and safety of Sintilimab plus CAPOX in the conversion
therapy for patients with unresectable locally advanced or limited metastatic adenocarcinoma
of the stomach or esophagogastric junction. The primary objectives are 12-month progression-
free survival (PFS) rate. Secondary objectives include safety, objective response rate (ORR),
R0 resection rate , tumor regression grading（TRG）, progression- free survival (PFS) ，overall
survival (OS) and exploratory biomarker assessment. Subjects enrolled are treated with oral
capecitabine 1000mg per m2 bid for two weeks（every 3 weeks）and intravenous oxaliplatin 130mg
per m2（every 3 weeks）in combination with sintilimab 200mg (every 3 weeks) for 3 cycles. After
3 cycles of treatment, the tumor was evaluated. The clinical efficacy was evaluated as
CR\PR\SD. Patients with SD,PR,CR will be treated with surgery. 36 patients will be included
in this study
1. Histologic and/or cytologic diagnosis of unresectable locally advanced or limited
metastatic adenocarcinoma of the stomach or esophagogastric junction.
2. Metastatic lesions are resectable or can be controlled by local ablative procedure.
3. Definition of limited metastatic status:
1. abdominal, retroperitoneallymphnodemetastases only (eg,para-aortic, intra
aortic-caval, peripancreatic, or mesenterial lymph nodes).
2. One incurable organ site with or without retroperitoneal lymph node metastases.
One incurable organ site metastases according to the following schema： -
Localized potentially operable peritoneal carcinomatosis or only cytology-
positive (Cy1) peritoneal lavage fluid without macroscopic peritoneal metastasis
- liver metastasis, and the number of liver metastasis ≤ 3 those are
- unilateral or bilateral Krukenberg's tumors in the absence of macroscopic
- unilateral or bilateral adrenal metastases
- Extra-abdominal lymph node metastases such as supraclavicular or cervical
lymph node involvement.
4. Tumor HER-2 is negative.
5. Age 18-75, gender unlimited.
6. Survival expectation ≥12 weeks.
7. Eastern Cooperative Oncology Group (ECOG) 0 or 1.
8. Not previously treated with any systemic treatment (including HER2 inhibitors), or who
have metastasis 6 months after the end of adjuvant chemotherapy or neoadjuvant
chemotherapy. (Note: the use of oxaliplatin in previous adjuvant or neoadjuvant
therapy should not exceed 800 mg/m2, and the treatment-related toxicity must be
restored to common terminology criteria for adverse events (CTCAE) level 1 of the
National Cancer Institute [NCI] before randomization.).
9. According to the recist1.1 standard, there is at least one measurable objective tumor
focus. The maximum diameter of spiral CT must be ≥ 1cm, and the maximum diameter of
normal CT or MRI must be ≥ 2cm, and it should be carried out within 28 days before
10. All eligible patients have adequate organ function. According to the following
laboratory test results (no blood transfusion, G-CSF or other medical support
treatment within 14 days before the drug administration). The laboratory test results
within 1 week before the study drug administration meet the following conditions:
(HGB≥90 g/L , PLT ≥75 × 10⁹ /L, WBC ≥ 3.0× 10⁹ /L, ANC ≥1.5× 10⁹ / L, TBI ≤1.5 times
UNL, Cr≤1.5 times the UNL, ALT and AST ≤2.5 times UNL（5 times UNL )in case of liver
11. Subjects with active hepatitis B or active hepatitis C must receive antiviral
treatment for at least 14 days before the administration of the first study drug, and
pass the detection of hepatitis B virus (HBV) DNA titer (no more than 500 IU / ml or
2500 copies [CPS] / ml) and hepatitis C virus (HCV) RNA (no more than the detection
limit of the detection method), which can be included in the group test, and are
willing to continue to receive effective antiviral treatment during the study period.
12. Patients participate voluntarily and sign written informed consent
1.Severe hepatorenal insufficiency or history of myocardial infarction (within 3 months).
2.5-year history of other malignancies(except skin basal cell carcinoma, cervical carcinoma
3.Subjects with active or previous autoimmune diseases or risks that may recur(eg：requiring
immunosuppressive therapy for organ transplantation). However, subjects with type I
diabetes, hypothyroidism requiring hormone replacement therapy only, or skin diseases
without systemic treatment (such as vitiligo, psoriasis, or alopecia) were allowed to enter
4.Have had interstitial lung disease or noninfective pneumonia, etc. symptoms of the
disease or previous lung history may hinder the assessment or management of lung toxicity
related to the study drug.
5.Before the first administration of the study drug and who had a history of active
tuberculosis infection more than one year ago were considered suitable for inclusion if
they were judged by the investigator to have no evidence of active tuberculosis at present.
6.Severe uncontrolled medical disease or acute infection (fever above 38 ℃ caused by
7.The combination of serious internal and external diseases, affecting organ function, the
researchers think it is not suitable to participate in this clinical trial.
8.Pregnant or lactating women or fertile (men or women with menopause less than 1 year) are
unwilling to take contraceptive measures.
9.Patients with a long history of chronic diarrhea or complete intestinal obstruction.
10.Subjects requiring systemic treatment with corticosteroids (> 10 mg / day equivalent of
prednisone) or other immunosuppressive drugs within 14 days prior to administration of the
study drug. Note: if there is no active autoimmune disease, it is allowed to use inhaled or
local steroid hormone, or adrenaline replacement therapy with equivalent dose of prednisone
≤ 10 mg per day. Short term (< 7 days) use of glucocorticoids for prophylactic treatment
(e.g. contrast agent allergy) or for treatment of non autoimmune diseases (e.g. delayed
type hypersensitivity caused by contact allergens) is allowed.
11.Have interstitial lung disease or noninfective pneumonia, etc. symptoms of the disease
or previous lung history may hinder the assessment or management of lung toxicity related
to the study drug.
12.Subjects who have received any antibody / drug (such as anti-PD-1, anti-PD- L1,
anti-CTLA-4, anti OX-40, anti-CD137, anti Tim-3, anti LAG-3 antibody, etc.) targeting
T-cell co regulatory protein (immunocheckpoint).
13.Subjects with a history of hypersensitivity or hypersensitivity to study drug
14.unable to take oral medicine.
15.Presence of immunodeficient disease or HIV infection.
16.Patients not suitable for this clinical trial determined by the investigator