Clinical trial NCT06454435: Conversion Therapy of Sintilimab in Combination With Fruquintinib and Chemotherapy Versus Sintilimab and Chemotherpay in Stage IV Gastric Cancer
Official title: Sintilimab Combined With Fruquintinib and Chemotherapy Versus Sintilimab and Chemotherapy for Conversion Therapy in Unresectable Stage IV Gastric Cancer: a National Multicenter Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Gastric Cancer
Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
First posted: 2024-06-12
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

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.

Primary outcomes:
measure: R0-surgery conversion rate
timeFrame: about 3 years
Secondary outcomes:
measure: Pathological complete response (pCR)
timeFrame: about 3 years
measure: Major pathological response rate (MPR)
timeFrame: about 3 years
measure: Rate of downstaging
timeFrame: about 3 years
measure: Objective response rate (ORR)
timeFrame: about 3 years
measure: Disease control rate (DCR)
timeFrame: about 3 years
measure: Overall survival (OS)
timeFrame: about 3 years
measure: Progression-free survival (PFS)
timeFrame: about 3 years
measure: Adverse event (AEs)
timeFrame: about 3 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
Study officials:
References: