Apatinib, Irinotecan and S-1 (ApaIRIS) in Treating Patients With Metastatic Pancreatic Cancer After AG Regimen

A Phase II, Single-arm Study to Evaluate The Safety and Efficacy of Apatinib Combined With Irinotecan and S-1 (ApaIRIS) in Treating Patients With Metastatic Pancreatic Cancer After Chemotherapy With Albumin-bound Paclitaxel Plus Gemcitabine Regimen

This is a single arm, open label Phase II clinical trial to evaluate the efficacy and safety of apatinib combined with irinotecan and S-1 (ApaIRIS) in treating Patients with metastatic pancreatic cancer after chemotherapy with albumin-bound paclitaxel plus gemcitabine regimen

While AG (albumin-bound paclitaxel + gemcitabine) is one of the preferred first-line chemotherapy for metastatic pancreatic cancer, we have to investigate possible therapeutic options after AG regimen. In this single arm, open-label clinical trial, metastatic pancreatic cancer patients will be received apatinib, irinotecan and S-1. Treatment repeats every 4 weeks until the disease recurrence or unacceptable toxicity, death or begin a novel therapeutic.

The efficacy and safety data will be assessed through PFS, OS, ORR and adverse effects as graded by CTC-AE 5.0.

Inclusion Criteria:

• Informed consent and willing to complete the study according to the protocol

• ECOG performance scale ≤ 2;

• Diagnosed as pancreatic adenocarcinoma by histology and cytology;

• Treatment of patients with advanced metastatic pancreatic cancer who have failed with AG (albumin and gemcitabine) regimen

• Baseline blood routine and biochemical indexes meet the following criteria:

  1. Blood routine examination criteria must be met: (no blood transfusion within 14 days)

     1. HB≥90g/L；
     2. ANC≥1.5×109/L；
     3. PLT≥80×109/L

  2. Biochemical tests are subject to the following criteria:

     1. BIL <1.25xULN ；
     2. ALT and AST<2.5ULN；
     3. Serum creatinine. Less than 1 times the upper limit of normal value, Endogenous creatinine clearance>50ml/min ( Cockcroft-Gault formula).

• The advanced pancreatic cancer pathology, with measurable lesions (spiral CT scan is more than 10 mm, according to the standard of RECIST 1.1);

• Life expectancy ≥ 12 weeks;

• Doctors believe that treatment can bring benefits to patients.

Exclusion Criteria:

• unwilling or unable to comply with the study protocol;
• Other or malignant tumors in the past or at the same time, except for cured skin basal cell carcinoma and cervical carcinoma in situ;
• Allergy to apatinib, S-1 raw materials and/or their excipients;
• Received VEGFR inhibitors, such as sorafenib, chougny for treatment;
• Have high blood pressure and antihypertensive drug treatment can not drop to normal range(systolic pressure >140 mmHg, diastolic blood pressure 90>mmHg);
• Suffering from coronary artery disease above grade I, grade I arrhythmia (including corrected QT interval prolongation male > 450 ms, women > 470 MS) and grade I heart insufficiency; urine protein positive patients.
• Renal insufficiency, patients with previous kidney disease, urine protein positive (urinary protein detection 2+ or above, or 24-hour urine protein quantitation > 1.0g);
• Has a variety of factors influencing oral drugs (such as unable to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction, etc.)
• Pregnant or lactating women;
• Coagulant function abnormality (INR>1.5、APTT>1.5 ULN) with bleeding tendency; Those with bleeding tendency (such as active ulcerative lesions in the stomach, fecal occult blood (++), vaginal and/or hematemesis within 3 months, hemoptysis) or lesions close to the large vessel site;
• Patients with a deficiency of dihydropyrimidine dehydrogenase are known;
• Evidence of any severe or uncontrolled systemic disease (eg, unstable or decompensated breathing, heart, liver or kidney disease, HIV infection, high blood pressure, severe arrhythmia, diabetes, massive active bleeding);
• Patients with a history of psychotropic substance abuse who are unable to quit or have a mental disorder;
• According to the investigator's judgment, there are other serious patients who are at risk to the patient's safety or affect the patient's accompanying disease.