Conversion Therapy of Sintilimab in Combination With Fruquintinib and Chemotherapy Versus Sintilimab and Chemotherpay in Stage IV Gastric Cancer

NCT ID: NCT06454435

Last Updated: 2024-06-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 158 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-30
• Study Completion Date: 2027-06-30

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.

Conditions

Gastric Cancer; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sintilimab + Fruquinitinib + S-1 plus nab-paclitaxel

Group Type: EXPERIMENTAL

Sintilimab + Fruquinitinib + S-1 plus nab-paclitaxel

Intervention Type: DRUG

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.

Sintilimab + S-1 plus nab-paclitaxel

Group Type: ACTIVE_COMPARATOR

Sintilimab + S-1 plus nab-paclitaxel

Intervention Type: DRUG

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.

Interventions

Sintilimab + 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.

Intervention Type: DRUG

Sintilimab + 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

Countries

China

Central Contacts

Han Liang, MD

Role: CONTACT

tjlianghan@126.com

18622221082

Facility Contacts

Han Liang, MD

Role: primary

tjlianghan@126.com

18622221082

Other Identifiers

E20231573

Identifier Type: -

Identifier Source: org_study_id