Clinical trial NCT04065282: The Purpose of This Study is to Evaluate the Efficacy and Safety of Sintilimab in Combination With Xelox as Neoadjuvant Therapy for Patients With Resectable Locally Advanced Gastric or Gastroesophageal Adenocarcinoma.
Official title: A Prospective, Multicenter, Single-armed, Phase II Study Evaluating Efficacy and Safety of Neoadjuvant Sintilimab in Combination With Capecitabine and Oxaliplatin (XELOX) in Patients With Resectable Locally Advanced Gastric or Gastroesophageal Adenocarcinoma.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Gastric Cancer
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
First posted: 2019-08-22
Enrollment: 36
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
Intervention model description: neoadjuvant chemotherapy sintilimab plus XELOX
Primary purpose: TREATMENT

Brief summary: Sintilimab in Combination With Capecitabine and Oxaliplatin (XELOX) as Neoadjuvant Therapy in patients With Resectable Locally Advanced Gastric Cancer

Detailed description: This prospective, multicenter, single-armed, phase II study will evaluate efficacy and safety of Sintilimab in combination with Xelox (Oxaliplatin 130mg/m2 iv d1 Q3w and Capecitabine 1000mg/m2 po Bid d1-14 Q3W) as neoadjuvant therapy in patients with resectable locally advanced gastric or gastroesophageal adenocarcinoma(G/GEJ AC). Newly diagnosed, treatment naïve patients with resectable locally advanced gastric or G/GEJ AC will be eligible to receive up to 3 cycles of sintilimab plus Xelox regimen as neoadjuvant therapy. Following radical gastrectomy will be performed within one to four weeks since last dosing for patients with resectable cancer after radiological evaluation.

Eligibility criteria: Inclusion Criteria:

1. Histologically proven adenocarcinoma of the stomach.
2. The primary tumor locates at stomach or esophagogastroesophageal ic junction.
3. Clinical T3-4NxM0 disease, confirmed by enhanced contrast abdominal computed tomography (CT) or magnetic resonance imaging (MRI).
4. At least one measurable lesion.
5. Resectable gastric or gastroesophageal cancer, judged by surgeons in this studyEligible and reasonably suitable for potentially curative resection
6. ECOG performance status 0-1.
7. Adequate organ function for chemotherapy and surgical treatment, as evaluated by laboratory tests.
8. Written (signed) informed consent.
9. Good compliance with the study procedures, including lab and auxiliary examination and treatment.
10. Agree to use an approved contraceptive method during the treatment period, until 120 days after last dose of Sintilimab or 180 days after last dose of chemotherapy.

Exclusion Criteria:

1. Unsectable primary tumor or any distant metastatic disease.
2. Received any anti-cancer therapy for this disease, including radiation therapies, chemotherapies, immunotherapies, and Chinese traditional herb therapies.
3. Clinical T1-2N0M0 disease, confirmed by CT/MRI or endoscopic ultrasonography.
4. Active autoimmune disease or history of refractory autoimmune disease.
5. History of any other malignant tumor within 2 years, excluding cured local tumor, such as resected skin basal cell or squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, or ductal carcinoma in situ (DCIS).
6. History of gastrointestinal hemorrhage within 2 weeks before enrollment or patients with a high risk of hemorrhage.
7. History of gastrointestinal perforation within 6 months before enrollment.
8. Gastrointestinal obstruction, gastrointestinal dysfunction, or malabsorption syndrome that may affect the absorption of Capecitabine.
9. Weight loss is greater than 20% within 2 months before enrollment.
10. History of severe pulmonary disease, including but not limited to interstitial pulmonary disease, noninfectious pneumonitis, pulmonary fibrosis, acute pulmonary disease
11. Uncontrolled systematic disease, including diabetes mellitus, hypertension, etc.
12. Severe chronic or active infectious disease that needs systematic antibiotics, antifungal, or antiviral therapies.
13. Untreated chronic hepatitis B, serum HBV DNA load higher than the lower threshold of the test, or HCV RNA positive.
14. With any cardiovascular risk factors as follow:

    1. History of angina within 28 days before enrollment, defined as moderate pain affecting daily activities;
    2. History of symptomatic pulmonary embolism within 28 days before enrollment;
    3. History of acute myocardial infarction within 6 months before enrollment;
    4. History of NYHA class III/IV heart failure within 6 months before enrollment;
    5. History of grade 2 (Lown grading system) or menopause ventricular arrhythmias or history of supraventricular arrhythmias that needs treatment within 6 months before enrollment;
    6. History of cerebrovascular accident within 6 months before enrollment;
15. grade 1 Peripheral neuropathy , excluding patients with only deep tendon reflex absence.\]
16. Known Dihydropyrimidine dehydrogenase (DPD) deficiency.
17. Known allergic to any drug used in this study.
18. History of allogeneic hematopoietic stem cell transplantation or organ transplantation.
19. Receiving corticosteroid (\> 10mg/d prednisone or equivalent dose of steroids) or other systematic immunosuppression therapies within 14 days before enrollment, excluding following therapies:

    1. steroid hormone replacement therapy (≤10mg/d);
    2. local steroid therapy;
    3. short-term, prophylactic steroid therapy for preventing allergies or nausea and vomiting
20. Receiving attenuated vaccine within 4 weeks before enrollment.
21. Receiving immunotherapy or other study drugs within 28 days before enrollment,
22. History of receiving anti-PD-1, anti-PD-L1, anti-PD-L2, or any other T cell co-simulation or checkpoint inhibitor therapy.
23. Receiving major surgery within 28 days before enrollment.
24. For patients with uncontrolled epilepsy, central nervous system disease, or mental disorder, researchers should evaluate if the inform consent and/or the compliance would be affected by their disease.
25. Any drug or alcohol abuse that would affect drug management or toxicity analysis.
26. Pregnant or nursing female.

Primary outcomes:
measure: Pathological complete response rate (pCR)
timeFrame: after surgical resection (up to 12 weeks after first dosing)
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: 9 to 12 weeks
measure: Tumor regression grade (TRG)
timeFrame: after surgical resection (up to 12 weeks after first dosing)
measure: Disease free survival (DFS)
timeFrame: every 90 days after resection, up to 2 years
measure: 1-year overall survival rate
timeFrame: 1 years
measure: 2-year overall survival rate
timeFrame: 2 years
Other outcomes:
measure: Overall survival (OS)
timeFrame: up to 5 years
measure: PD-L1 expression, tumor infiltrating lymphocytes (TIL), etc.
timeFrame: after surgical resection (up to 12 weeks after first dosing)
measure: Cytokine (IL-6)
timeFrame: up to 12 weeks after first dosing
measure: immune cell subpopulation (CD3, CD4, CD8 lymphocytes )
timeFrame: up to 12 weeks after first dosing
Locations:
city: Zhejiang
country: China
facility: First Affiliated Hospital of Zhejiang University
Study officials:
References:
citation: Jiang H, Yu X, Li N, Kong M, Ma Z, Zhou D, Wang W, Wang H, Wang H, He K, Li Z, Lu Y, Zhang J, Zhao K, Zhang Y, Xu N, Li Z, Liu Y, Wang Y, Wang Y, Teng L. Efficacy and safety of neoadjuvant sintilimab, oxaliplatin and capecitabine in patients with locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: early results of a phase 2 study. J Immunother Cancer. 2022 Mar;10(3):e003635. doi: 10.1136/jitc-2021-003635.