Clinical trial NCT04101929: Apatinib, Irinotecan and S-1 (ApaIRIS) in Treating Patients With Metastatic Pancreatic Cancer After AG Regimen
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Pancreatic Cancer
Keywords: metastatic pancreatic cancer
pancreatic adenocarcinoma
apatinib
S-1
irinotecan
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2019-09-24
Enrollment: 126
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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Overall Survival
timeFrame: through study completion, an average of 1 year
measure: Incidence of Adverse Events
timeFrame: through study completion, an average of 1 year
measure: Overall Response Rate
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University
state: Shanghai
Study officials:
affiliation: Fudan University
name: Xian-Jun Yu
role: STUDY_DIRECTOR
References: