A Multicenter, Prospective, Open-label, Randomized Controlled, Phase II Clinical Trial Comparing the Efficacy of Sintilimab Plus Nab-POF Regimen, Sintilimab Plus XELOX Chemotherapy, and Lenvatinib, Sintilimab Plus XELOX Chemotherapy in the Treatment of HER2-negative, Metastatic Gastric Cancer
Overview
- Phase
- Phase 2
- Intervention
- Sintilimab, oxalipaltin, 5FU,Nab-paclitaxel,lenvatinib
- Conditions
- Gastric (Stomach) Cancer
- Sponsor
- Fudan University
- Enrollment
- 141
- Locations
- 2
- Primary Endpoint
- Objective response rate
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
This trial is a prospective, open, randomized, phase II clinical study. It compares the current first-line treatment for advanced gastric cancer in phase II clinical trials, with the best efficacy being the combination of orient-16 study with sintilimab and XELOX regimen. The purpose of this study is to evaluate whether adding anti-angiogenic drugs or chemotherapy drugs on the basis of two-drug chemotherapy regimen (XELOX regimen) and PD-1 monoclonal antibody can improve efficacy for advanced gastric cancer.
Investigators
Weijian Guo
chief physician
Fudan University
Eligibility Criteria
Inclusion Criteria
- •Males or females aged over than 18 years
- •Histologically or cytologically confirmed gastric adenocarcinoma (including GEJ adenocarcinoma)
- •Presence of measurable lesions(RECIST 1.1)
- •Newly diagnosed patients; or patients with recurrence after surgery, who have been off adjuvant chemotherapy for at least 6 months and have not received any anti-cancer treatment within the past 6 months
- •ECOG PS score: 0-1
- •Expected survival over than 3 months
- •Normal major organ function or reserve, meeting the following criteria (determined by laboratory test data within 7 days (inclusive) before screening): HB ≥90 g/dL, ANC ≥1.5×109/L, PLT ≥100×109/L; BIL\<1.5×ULN, ALT and AST \<2.5×ULN, if with metastases to liver, then ALT, AST \<5×ULN; serum Cr≤1×ULN, endogenous creatinine clearance \>50 mL/min (calculated by CK formula), international normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN, if the subject is receiving anticoagulant therapy, PT should be within the intended range of the anticoagulant drug
- •Subjects who voluntarily participate in this study, sign the informed consent form, have good compliance, and cooperate with follow-up
Exclusion Criteria
- •Histopathological assessment of HER2 positivity (immunohistochemistry 3+ or immunohistochemistry 2+ and FISH positive)
- •Known dMMR/MSI-H
- •History of other malignant neoplasms within 3 years prior to enrollment, except for cured cervical carcinoma in situ or basal cell carcinoma
- •Presence of brain metastases to meninges
- •Malignant pleural or peritoneal effusion
- •Presence of gastrointestinal obstruction, gastrointestinal haemorrhage (fecaloccult blood +++ or higher), or perforation
- •Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2, CD137, CTLA-4 antibodies, or any other antibody or drug specifically targeting T-cell co-stimulatory or checkpoint pathways
- •Subjects with active or history of autoimmune diseases that might relapse (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disorder, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or high-risk patients (e.g., those requiring immunosuppression after organ transplant), except for those with vitiligo, psoriasis, alopecia, or Graves' disease that have not required systemic treatment within the past 2 years, or hypothyroidism requiring only thyroid hormone replacement therapy, or Type I diabetes mellitus requiring only insulin replacement therapy
- •Current interstitial lung disorder or pneumonia, pulmonary fibrosis, acute lung disorder, or radiation pneumonitis
- •Participation in other drug clinical studies within 4 weeks prior to the first dose (based on the use of investigational drug), except observational (non-interventional) clinical studies
Arms & Interventions
XELOX regimen plus sintilimab
sintilimab 200mg ivgtt d1+oxaliplatin 130mg/m2 ivgtt d1+xeloda 1000mg/m2 bid po d1-14，q3w
Intervention: Sintilimab, oxalipaltin, 5FU,Nab-paclitaxel,lenvatinib
Nab-POF regimen plus sintilimab
sintilimab (200mg for the first time, 100mg for the second time, in alteration) ivgtt d1+oxaliplatin 85mg/m2 ivgtt d1+Nab-paclitaxel 125 mg/m2 ivgtt d1+5FU 2.4g/m2 civ48h, q2w
Intervention: Sintilimab, oxalipaltin, 5FU,Nab-paclitaxel,lenvatinib
XELOX regimen plus sintilimab plus lenvatinib
sintilimab 200mg ivgtt d1+oxaliplatin 130mg/m2 ivgtt d1+xeloda 1000mg/m2 bid po d1-14+lenvatinib 8mg(\<60kg) or 12mg(≥60kg) po qd，q3w
Intervention: Sintilimab, oxalipaltin, 5FU,Nab-paclitaxel,lenvatinib
Outcomes
Primary Outcomes
Objective response rate
Time Frame: the duration from the date of randomization to any documented tumor progression or death due to any cause，assessed up to 24 months
he proportion of patients whose tumor decrease to a certain size and remained for a certain period of time, including those with complete response (CR) and partial response (PR)
Secondary Outcomes
- Overall survival(the duration from the date of randomization to the date of death due to any cause,assessed up to 48 months)
- Progression-free survival time(the duration from the date of randomization to any documented tumor progression or death due to any cause, assessed up to 48 months)
- Disease control rate(the duration from the date of randomization to any documented tumor progression or death due to any cause, assessed up to 24 months)