Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

• Status: Not yet recruiting
• Trial end date: 2021-10-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sichuan University
• Treatments: Capecitabine; Oxaliplatin

Criteria

Inclusion Criteria:

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 potentially resetabl.

• unilateral or bilateral Krukenberg's tumors in the absence of macroscopic peritoneal carcinomatosis.

• 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 enrollment.

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 metastasis.

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

Exclusion Criteria:

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 in situ).

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 the group.

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 infection).

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 components.

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