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

NCT06748508 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: MGC-NabPOF
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 2

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.

Conditions

Gastric (Stomach) Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  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)

  the duration from the date of randomization to any documented tumor progression or death due to any cause，assessed up to 24 months

Secondary Outcomes (3)

• 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

Study Arms (3)

XELOX regimen plus sintilimab

ACTIVE COMPARATOR

sintilimab 200mg ivgtt d1+oxaliplatin 130mg/m2 ivgtt d1+xeloda 1000mg/m2 bid po d1-14，q3w

Drug: Sintilimab, oxalipaltin, 5FU,Nab-paclitaxel,lenvatinib

Nab-POF regimen plus sintilimab

EXPERIMENTAL

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

Drug: Sintilimab, oxalipaltin, 5FU,Nab-paclitaxel,lenvatinib

XELOX regimen plus sintilimab plus lenvatinib

EXPERIMENTAL

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

Drug: Sintilimab, oxalipaltin, 5FU,Nab-paclitaxel,lenvatinib

Interventions

Sintilimab, oxalipaltin, 5FU,Nab-paclitaxel,lenvatinib DRUG

Patients were randomized in a 1:1:1 ratio to three treatment groups: control group A: pembrolizumab combined with XELOX regimen, the regimen was repeated every 3 weeks, and tumor efficacy was evaluated every 2 treatment cycles. Group B: treatment regimen was pembrolizumab combined with Nab-POF regimen, the regimen was repeated every 2 weeks, and tumor efficacy was evaluated every 3 treatment cycles. Group C: treatment regimen was pembrolizumab combined with XELOX regimen and lenvatinib, the regimen was repeated every 3 weeks, and tumor efficacy was evaluated every 2 treatment cycles.

Also known as: xeloda

Nab-POF regimen plus sintilimab; XELOX regimen plus sintilimab; XELOX regimen plus sintilimab plus lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Use of immunosuppressant drugs within 4 weeks prior to the first dose of study treatment, excluding nasal, inhaled, or other topical glucocorticoids or physiological doses of systemic glucocorticoids (i.e., no more than 10 mg/day of prednisone or equivalent dose of other glucocorticoids), or short-term (no more than 7 days) use of glucocorticoids for the prevention or treatment of non-autoimmune allergic diseases
• Receipt of live attenuated vaccines within 4 weeks prior to the first dose of study treatment or planned immunization during the study period. Note: Inactivated seasonal influenza vaccines for injection are allowed within 4 weeks prior to the first dose; however, live attenuated influenza vaccines are not allowed.
• Major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of study treatment or anticipated need for major surgery (not related to this study) during the study treatment period.
• History of human immunodeficiency virus (HIV) infection (i.e., HIV antibody positive), or other acquired or congenital immunodeficiency diseases, or history of organ transplant or stem cell transplant
• Active chronic hepatitis B or active hepatitis C; hepatitis B virus carriers, but patients with stable hepatitis B viral loads after drug therapy (HBV DNA ≤ 200 IU/mL or copy number \< 1000 copies/mL), and patients who have cleared hepatitis C virus (HCV RNA negative) are eligible for enrollment

Sponsors & Collaborators

• Fudan University: lead

Study Sites (2)

Fudan University Cancer Hospital

Shanghai, Shanghai Municipality, 200032, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

sintilimab; lenvatinib; Capecitabine

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Weijian Guo, Ph.D., M.D.

CONTACT

+86 021-64175590; guoweijian1@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: December 3, 2024
• First Posted: December 27, 2024
• Study Start: December 25, 2024
• Primary Completion (Estimated): July 25, 2027
• Study Completion (Estimated): December 25, 2027
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)