Clinical trial NCT05177068: Conversion Therapy of Fruquintinib in Combination With Sintilimab and SOX in Unresectable Gastric Cancer
Official title: A Phase II Clinical Study of Fruquintinib Combined With Sintilimab and SOX as Conversion Therapy of Potentially Resectable Stage IV Gastric Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Gastric Cancer
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2022-01-04
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase II study to evaluate the efficacy and safety of combination of fruquintinib (VEGFR 1/2/3 inhibitor), sintilimab (PD-1 inhibitor) and SOX conversion therapy in unresectable advanced gastric cancer patients.

Detailed description: Eligible patients will be given 3 or 6 cycles of combined therapy of fruquintinib + sintilimab + SOX. Then the patients evaluated resectable will be given one additional cycle of combined treatment with sintilimab + SOX, followed by R0 resection. If evaluated unresectable after 6 cycles of combination therapy, the patient will be given palliative first-line treatment. Adjuvant treatment with SOX regimen will be started 4 weeks after R0 resection for a total of 8 cycles in the perioperative period.

Eligibility criteria: Inclusion Criteria:

* Signed the Informed Consent Form
* Ages: 18-75 Years (concluding 18 and 75 Years)
* Pathologically confirmed gastric/gastroesophageal junction adenocarcinoma, and meets one of the following conditions: invasion of adjacent organs such as colon, tail of pancreas and spleen; localized peritoneal metastasis; positive exfoliative cytology of ascites; class I, class II, part of class III and very few class IV stage IV gastric adenocarcinoma according to biological behavior; N3; extensive or fused lymph node metastasis; Krukenberg tumor; Liver metastasis limited to one lobe, less than 5cm in diameter, isolated abdominal aortic metastasis, etc;
* Untreated(e.g. radiotherapy, chemotherapy, target therapy and immunotherapy)
* Life expectancy greater than 3 months
* ECOG(Eastern Cooperative Oncology Group) :0\~1
* Sufficient organ and bone marrow functions as follows:

  1. Absolute Neutrophil Count (ANC) ≥1.5×109/L, White Blood Cell≥3.5×109/L;
  2. Platelet Count of ≥100×109/L;
  3. Hemoglobin≥90g/L;
  4. Total Bilirubin (TBIL) ≤1.5 x ULN;
  5. ALT and AST\<2.5 x ULN, GPT≤1.5×ULN; If there is liver metastasis, then ALT and AST\<5.0 x ULN, GPT≤3.0×ULN;
  6. Serum Creatinine (SCr) ≤1.0×ULN;
  7. Endogenous creatinine clearance rate \> 60ml / min (Cockcroft Gault formula);
* No severe dysfunction of heart, lung and liver; No jaundice and gastrointestinal obstruction; No acute infection
* Not participating in other clinical trials 4 weeks before and during the treatment

Exclusion Criteria:

* Known HER-2 positive
* Distal metastasis to lung, brain, and bone
* Have received operation on the stomach
* A history of other malignancies within 5 years prior to inclusion, except for cervical carcinoma in situ, basal or squamous cell skin cancer
* Patients with any active autoimmune disease or a documented history of autoimmune disease within 4 weeks prior to enrollment
* Previously received allogeneic bone marrow transplantation or organ transplantation
* Known hypersensitivity to any of the study drugs or excipients
* Hypertension that is not controlled by the drug, and is defined as: SBP ≥150 mmHg and/or DBP ≥90 mmHg
* International normalized ratio (INR) \> 1.5 or partially activated prothrombin time (APTT) \> 1.5 × ULN
* Poorly controlled diabetes before enrollment
* Clinically significant electrolyte abnormalities judged by researchers
* With any diseases or conditions that affected drug absorption, or the patient could not take drugs orally
* Patients with obvious evidence of bleeding tendency or medical history within 3 months before enrollment, hemoptysis or thromboembolism within 12 months
* Cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe / unstable angina pectoris or coronary artery bypass grafting within 6 months before enrollment; Congestive heart failure, New York Heart Association (NYHA) grade \> 2; ventricular arrhythmia requiring drug treatment; LVEF (left ventricular ejection fraction) \< 50%
* Active infection or serious infection that is not controlled by drug (≥CTCAE v5.0 Grade 2）
* History of clinically significant hepatic disease, including, but not limited to, known hepatitis B virus (HBV) infection with HBV DNA positive (copies ≥1×104/ml); known hepatitis C virus infection with HCV RNA positive (copies ≥1×103/m)
* Women who are pregnant or lactating
* Urinary protein ≥ ++, and the 24-hour urine protein quantification is greater than 1.0 g
* Have any other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other conditions which, according to judgement of the investigator, renders the patient inappropriate for using of the investigational product or may affect interpretation of study results
* Patients considered unsuitable for inclusion in this study by the investigator.

Primary outcomes:
measure: Surgical complete resection rate (R0)
timeFrame: about 3 years
Secondary outcomes:
measure: Rate of downstaging
timeFrame: about 3 years
measure: Pathological complete response (pCR) rate
timeFrame: about 3 years
measure: Major pathological response (MPR)
timeFrame: about 3 years
measure: Objective Response Rate (ORR)
timeFrame: about 3 years
measure: Progression-free survival (PFS)
timeFrame: about 3 years
measure: Overall survival (OS)
timeFrame: about 3 years
measure: adverse event (AEs)
timeFrame: about 3 years
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan Tumor Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Tumor Hospital
state: Henan
Study officials:
References: