Gastric Adenocarcinoma, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma
Conditions
Brief summary
This is a multicenter, randomized, open-label, phase 2 clinical study aiming to evaluate the feasibility and efficacy of sintilimab (PD-1 inhibitor) in combination of fruquintinib and chemotherapy (S-1 plus nab-paclitaxel) versus sintilimab and chemotherapy as conversion therapy in patients with stage IV gastric cancer in China.
Interventions
DRUGSintilimab + Fruquinitinib + S-1 plus nab-paclitaxel
Drug: Sintilimab Sintilimab 200mg, D1, IV, Q3W 4-8 cycles Drug: Fruquintinib Fruquinitinib 4mg/d, QD, PO, D1-D14, Q3W 4-8 cycles Drug: S-1 BSA\<1.25 m2, 40mg twice/day; BSA 1.25-1.5m2, 50mg twice/day; BSA≥1.5 m2, 60mg twice/day, po, D1-D14, Q3W 4-8 cycles Drug: Nab-paclitaxel * without peritoneal metastases: 260 mg/m2, IV, D1 for 3h, Q3W 4-8 cycles; * with peritoneal metastases: 80mg/m2 IP, plus 180mg/m2, IV, D1, Q3W 4-8 cycles.
DRUGSintilimab + S-1 plus nab-paclitaxel
Drug: Sintilimab Sintilimab 200mg, D1, IV, Q3W 4-8 cycles Drug: S-1 BSA\<1.25 m2, 40mg twice/day; BSA 1.25-1.5m2, 50mg twice/day; BSA≥1.5 m2, 60mg twice/day, po, D1-D14, Q3W 4-8 cycles Drug: Nab-paclitaxel * without peritoneal metastases: 260 mg/m2, IV, D1 for 3h, Q3W 4-8 cycles; * with peritoneal metastases: 80mg/m2 IP, plus 180mg/m2, IV, D1, Q3W 4-8 cycles.
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed gastric/gastroesophageal junction adenocarcinoma through gastroscopy. * Ages: 18-70 Years (concluding 18 and 70 Years) * Life expectancy ≥3 months. * Treatment-naive Stage IV (clinical staging, AJCC 8th) unresectable patients, no prior antitumor therapy (including radiation, chemotherapy, targeted therapy or immunotherapy, etc.). * The Eastern Cooperative Oncology Group Performance status (ECOG PS) of 0-1. * Preoperative examinations using CT, MRI, PET-CT, etc., indicating only one unresectable factor OR peritoneal metastasis with another unresectable factor, such as: 1. N3 lymph node metastasis, mainly referring to group 16 lymph node metastasis. 2. Extensive or bulky lymph nodes (D2) 3. Locally advanced T4b. 4. Hepatic metastases (H1): ≤5 lesions with a total diameter ≤8cm. 5. Peritoneal metastasis (CY1, P1). 6. Ovarian metastasis (Krukenberg tumor). * Physically fit for major abdominal surgery. * Adequate organ and marrow function, defined as: 1. Hematological status: Absolute neutrophil count (ANC) ≥1.5×10\^9/L; Platelet count (PLT) ≥100×10\^9/L; Hemoglobin (HGB) ≥9.0 g/dL. 2. Liver function: For patients without liver metastasis, serum total bilirubin (TBIL) ≤1.5× upper limit of normal (ULN); ALT and AST ≤2.5×ULN. For patients with liver metastasis: TBIL ≤1.5×ULN; ALT and AST ≤5×ULN. 3. Renal function: Creatinine clearance (Ccr) ≥50 mL/min (calculated using the Cockcroft/Gault formula). * Adequate coagulation function, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 times ULN. * Voluntary participation and signed informed consent with expected good compliance and follow-up. * Not involved in other clinical trials. * Willing to provide blood and histological samples. * No serious conditions affecting anesthesia, or surgery. * No hematologic disorders affecting postoperative hemoglobin levels.
Exclusion criteria
* Has distal metastases other than oligometastases as defined in the inclusion criteria, such as pulmonary metastases, brain metastases, bone metastases, etc. * HER-2 positive patients or willing to receive Trastuzumab. * Endoscopic signs of active bleeding from the lesion. * Patients with moderate/large volume of ascites. * Near-obstruction at the cardia or pylorus affecting feeding and gastric emptying or difficulty swallowing tablets. * Concurrently suffering from other serious illnesses that are difficult to control (Severe uncontrolled recurrent infections, atrial fibrillation, angina pectoris, cardiac insufficiency, ejection fraction measurement under 50%, uncontrolled hypertension, renal insufficiency, symptomatic peripheral neuropathy, and NCI classification \>II) * Has already on other medications prior to enrollment or could not be assured of compliance after enrollment. * Allergy to any drugs in the regimen. * Women who are pregnant or breastfeeding and have childbearing potential but are not taking adequate contraceptive measures. * Organ transplant recipients requiring immunosuppression. * Patients without decision-making capacity or with psychiatric disorders. * Systemic treatment with Chinese herbal anti-tumor or immunomodulatory drugs (including thymosin, interferons, interleukins) within 2 weeks before the first dose. * Use of immunosuppressive drugs within 4 weeks before the first study treatment, excluding local steroids or physiological doses of systemic steroids. * Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment. * Has a diagnosis of autoimmune disease within the previous 2 years (Patients with vitiligo, psoriasis, alopecia areata, or Graves' disease who do not require systemic therapy within the last 2 years, hypothyroidism requiring only thyroid hormone replacement therapy, and type I diabetes mellitus requiring only insulin replacement therapy are eligible for enrollment). * Known history of primary immunodeficiency. * Known to have active tuberculosis. * Has history of human immunodeficiency virus (HIV) infection (i.e., HIV antibody . positive); untreated acute or chronic active hepatitis B or hepatitis C infection. Patients receiving antiretroviral therapy are eligible for enrollment on an individual basis as determined by the physician with monitoring of viral copy number. * Urinalysis indicating urine protein ≥2+ and 24-hour urine protein quantification \>1.0g.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| R0-surgery conversion rate | about 3 years | The proportion of patients who underwent R0 surgery among all efficacy evaluable patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major pathological response rate (MPR) | about 3 years | The proportion of patients with a major pathological response (≤10% residual viable tumor) at the time of definitive surgery among all patients who underwent conversation surgery. |
| Rate of downstaging | about 3 years | To determine the rate of ypT0 and ypN0, and downstaging ratio of preoperative imaging clinical stage compared with baseline. |
| Objective response rate (ORR) | about 3 years | The proportion of patients who achieved complete response (CR) or partial response(PR) per RECIST v1.1. |
| Pathological complete response (pCR) | about 3 years | The proportion of patients with a pathological complete response (ypT0&N0) at the time of definitive surgery among all patients who underwent conversation surgery. |
| Overall survival (OS) | about 3 years | The time from the initial date of conversation therapy to the date of death due to any cause. |
| Progression-free survival (PFS) | about 3 years | The time from the initial date of conversation therapy to the date of first documentation of disease progression or death due to any cause, whichever occurs first. |
| Adverse event (AEs) | about 3 years | Toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Incidence and grade of surgery-related complications will also be as assessed. |
| Disease control rate (DCR) | about 3 years | The proportion of patients who achieved CR, PR or stable disease(SD) per RECIST v1.1. |
Countries
China
Contacts
Primary ContactHan Liang, MD
Outcome results
None listed