Neoadjuvant of Sintilimab Combined Weekly Metronomic Chemotherapy (PLOF) for Resectable Locally Advanced Gastric Cancer

NCT06054906 | Recruiting Phase 2

• 1 other identifier: KY2022-1018
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate efficacy and safety of Neoadjuvant of Sintilimab Combined Weekly Metronomic Chemotherapy (PLOF) in resectable locally advanced gastric cancer.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of participants with no residual surviving tumor cells in resection specimens and lymph nodes

  Pathological complete response rate (pCR), defined as the proportion of participants with no residual viable tumor cells on microscopy and negative lymph nodes as a percentage of all participants. We will evaluate pathological complete response rate of primary tumor and locally metastatic lymph nodes after 6 weeks of neoadjuvant therapy.

  up to 6 weeks after first dosing

• Percentage of participants with ≤10% tumor cell survival in resection specimens

  Major pathologic response (MPR) rate, defined as the proportion of participants with ≤10% surviving tumor cells in the resection specimen as a percentage of all participants. We will evaluate major pathological response rate of primary tumor and locally metastatic lymph nodes after 6 weeks of neoadjuvant therapy.

  up to 6 weeks after first dosing

Secondary Outcomes (5)

• Percentage of participants achieving complete remission (CR) and partial remission (PR) after treatment

  2 to 6weeks after the end of treatment

• Percentage of participants achieving remission (PR+CR) and lesion stabilization (SD) after treatment

  2 to 6weeks after the end of treatment

• 2-year progression-free survival (PFS) rate

  From enrollment to study completion, assessed up to 2 years

• 3-year overall-survival (OS) rate

  From enrollment to study completion, assessed up to 3 years

• Number of participants with treatment-related adverse events as assessed by NCI-CTC

  From enrollment to study completion, assessed up to 3 years

Other Outcomes (4)

• Number of immune cells in peripheral blood

  From enrollment to study completion, assessed up to 3 years

• Proportion of immune cells in peripheral blood

  From enrollment to study completion, assessed up to 3 years

• Number of immune cells in tumor tissues

  From enrollment to study completion, assessed up to 3 years

Study Arms (1)

sintilimab+metronomic PLOF

EXPERIMENTAL

sintilimab therapy(200mg, iv,d1,Q3W, 2cycles)and PLOF chemotherapy (Paclitaxel 60 mg/m2, oxaliplatin 50 mg/m2, 5-fluorouracil 425mg/m2, d1, QW, 6cycles) followed by adjuvant sintilimab therapy(200mg, iv,d1,Q3W, 2cycles)and PLOF chemotherapy (Paclitaxel 60 mg/m2, oxaliplatin 50 mg/m2, 5-fluorouracil 425mg/m2, d1, QW, 6cycles) neoadjuvant chemotherapy (8 weeks) preceding surgery (3 weeks after completion of chemotherapy) followed by adjuvant chemotherapy (16 weeks, begin within 12 weeks after surgery)

Drug: sintilimab+metronomic PLOF

Interventions

sintilimab+metronomic PLOF DRUG

Drug: Sintilimab 200mg iv d1 Q3W, 2cycles Drug: Paclitaxel 60 mg/m2, d1, QW,6cycles Drug: Oxaliplatin 50 mg/m2, d1, QW, 6cycles Drug: 5-fluorouracil 425mg/m2 ,d1 ,QW, 6cycles

sintilimab+metronomic PLOF

Eligibility Criteria

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

You may qualify if:

• Signed written Informed Consent Form
• Male or female, age ≥ 18 years old
• Histologically confirmed gastric adenocarcinoma, diagnosed as locally progressive according to the AJCC 8th ed, cTNM diagnosis of cT3-4aN1-3M0 and resectable lesion as assessed by the investigator
• No prior systemic therapy such as surgery, radiotherapy, or immunotherapy for the disease at hand
• Consent to radical surgical treatment and no contraindications to surgery as determined by the surgeon
• ECOG PS: 0-1 score
• Expected survival \> 6 months
• Adequate organ function, must meet the following laboratory specifications:
• Absolute neutrophil count (ANC) ≥ 1.0x10\^9/L; 8.2 Platelets ≥ 80x10\^9/L; 8.3 Hemoglobin \> 7g/dL; 8.4 Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (Total bilirubin \> 1.5 x ULN but direct bilirubin ≤ ULN are allowed to be enrolled); 8.5 AST, ALT ≤ 2.5×ULN; 8.6 Blood creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 ml/min; 8.7 INR or PT ≤ 1.5 times ULN; 8.8 TSH within normal range (Enrollment allowed if baseline TSH is outside normal range but FT4 is within normal range); 8.9 Myocardial enzyme profile within normal range;
• Negative pregnancy test in women of childbearing age
• Need to use contraception with an annual failure rate of less than 1% if there is a risk of conception

You may not qualify if:

• Endoscopically show signs of active bleeding from the lesion
• Current participation in an interventional clinical study or treatment with another investigational drug or use of an investigational device within 4 weeks prior to the first dose of study drug
• Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or agents targeting CTLA-4, OX-40, CD137, etc.
• Diagnosis of a malignant disease other than gastric cancer within 5 years prior to the first dose of therapy
• Active autoimmune disease requiring systemic therapy within 2 years prior to the first dose of the drug
• Live vaccination within 30 days prior to the first administration of the drug
• Have received systemic systemic therapy with proprietary Chinese medicines with antitumor indications or immunomodulatory drugs within 2 weeks prior to the first administration of the drug
• Have received systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment
• Has not fully recovered from any intervention-induced toxicity and/or complications (excluding malaise or alopecia) prior to initiation of therapy
• Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation
• Known hypersensitivity to drugs used in this study
• Known history of HIV infection
• Untreated active hepatitis B
• Active HCV infection
• Pregnant or lactating women

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (1)

Huashan Hospital, Fudan University

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: September 26, 2023
• Study Start: October 18, 2023
• Primary Completion: June 30, 2025
• Study Completion: December 31, 2025
• Last Updated: December 30, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)