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
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Fudan University
- Enrollment
- 126
- Locations
- 1
- Primary Endpoint
- Progression Free Survival
Study Overview
Brief Summary
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
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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:
- •Blood routine examination criteria must be met: (no blood transfusion within 14 days)
- •ANC≥1.5×109/L；
- •PLT≥80×109/L
- •Biochemical tests are subject to the following criteria:
- •BIL <1.25xULN ；
- •ALT and AST<2.5ULN；
- •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.
Arms & Interventions
Experimental: Apatinib + S-1+ Irinotecan
Apatinib: 250mg po qd； S-1 capsule: According to the body surface area <1.25m2 60mg/d, 1.25 ~ 1.5 m2 80 mg/d, > 1.5m2 100mg/d po bid, taking 7 days, stopping for 7 days, 28 days for 1 cycle; Irinotecan: According to the body surface area of 180 mg/m2, ivgg/90min, once every two weeks.
Intervention: Apatinib (Drug)
Experimental: Apatinib + S-1+ Irinotecan
Apatinib: 250mg po qd； S-1 capsule: According to the body surface area <1.25m2 60mg/d, 1.25 ~ 1.5 m2 80 mg/d, > 1.5m2 100mg/d po bid, taking 7 days, stopping for 7 days, 28 days for 1 cycle; Irinotecan: According to the body surface area of 180 mg/m2, ivgg/90min, once every two weeks.
Intervention: S-1 capsule (Drug)
Experimental: Apatinib + S-1+ Irinotecan
Apatinib: 250mg po qd； S-1 capsule: According to the body surface area <1.25m2 60mg/d, 1.25 ~ 1.5 m2 80 mg/d, > 1.5m2 100mg/d po bid, taking 7 days, stopping for 7 days, 28 days for 1 cycle; Irinotecan: According to the body surface area of 180 mg/m2, ivgg/90min, once every two weeks.
Intervention: Irinotecan (Drug)
Outcomes
Primary Outcomes
Progression Free Survival
Time Frame: through study completion, an average of 1 year
To investigate the progression-free survival (PFS) of patients with advanced metastatic pancreatic cancer who have failed with AG (albumin and gemcitabine) regimen after treatment with Apatinib combined with Irinotecan and S-1 (ApaIRIS)
Secondary Outcomes
- Overall Survival(through study completion, an average of 1 year)
- Incidence of Adverse Events(through study completion, an average of 1 year)
- Overall Response Rate(through study completion, an average of 1 year)
Investigators
Xian-Jun Yu
Prinicipal Investigator, Clinical Professor
Fudan University