Clinical trial NCT03258034: A Feasibility Study for Convernsion Therapy Using S1/Paclitaxel Chemotherapy Plus Apatinib in ELM Gastric Cancer
Official title: Phase II Study of Convernsion Therapy Using S1/Paclitaxel Chemotherapy Plus Apatinib in ELM Gastric Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Gastric Cancer
Keywords: Conversion therapy
Lead sponsor: The First Affiliated Hospital of Zhejiang Chinese Medical University
Sponsor class: OTHER
Collaborators: name: Zhejiang Cancer Hospital
name: Fujian Cancer Hospital
First posted: 2017-08-22
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The prognosis of Extensive lymph nodes metastatic(ELM) gastric cancer is poor. Chemotherapy occasionally converts it to a resectable cancer. Previous studies showed patients with ELM gastric cancer may obtain a survival benefit from chemotherapy and subsequent curative surgery. The key of conversion therapy of ELMGC is the high response rate. Apatinib, a novel targeted inhibitor of VEGF receptor 2 (VEGFR2), shows significant antitumor activity in the patients with GC. On the basis of our previous Ahead-G325 study, The purpose of this study is to investigate the efficacy and safety of S1/Paclitaxel chemotherapy plus Apatinib in the conversion therapys of ELM gastric cancer.

Detailed description: The investigators will apply SPA regimen for coversional therapy to abtain high response rate. Paclitaxel：150 mg/m2 i.v.3h , given on the first day. Apatinib, oral ,initial dose :425mg, QD, after meal ( try to take the medicine at the same time of the day ). Dose adjustment: Down-regulate the dosage to 250 mg per day at the first time. If the patient totally recovers from the toxic reaction after the regulation, we could up-regulate the dosage back to the former level. If the downregulation occurs again according to the protocol , then the up-regulation will be forbidden.

S-1 dosage: According to the body surface area, the initial dosage of S-1 is decided by the following criteria. Take the medicine twice daily (after breakfast and supper) for 2 weeks, then suspend for 1 week. Preventive medication: To prevent serious allergic reaction of Paclitaxel, preventive medication should be given in advance. We usually give dexamethasone 20mg orally 12 and 6 hours before the Paclitaxel, and diphenhydramine (or something analogous) 50 mg, cimetidine 300mg (or ranitidine 50mg) I.V. 30-60 minutes before the Paclitaxel. Repeat the therapeutic schedule every 3 weeks. 3-4 cycles of neoadjuvant chemotherapy before surgery, stop Apatinib in the last cycle.4 cycles of adjuvant chemotherapy including S-1 and Apatinib 4 to 6 weeks after surgery.

Eligibility criteria: Inclusion Criteria:

* ELM gastric cancer as proven histologically under following condition: unable radical excision due to the abdominal aorta a2-b1 or extensive lymph nodes metastatic,
* Definitely diagnosed as above stage of gastric cancer before operation via CT of MRI, ultrasonic endoscopy, PET-CT, or through the laparoscopic exploration if necessary
* Untreated (e.g. radiotherapy, chemotherapy, target therapy and immunotherapy)
* Negative HER-2 state
* ECOG(Eastern Cooperative Oncology Group): 0\~2
* Age: 18\~70 years old- survival time \> 3monts
* Normal hemodynamic indices before the recruitment(including blood cell count and liver/kidney function ). For example: WBC\>4.0\*109/ L, NE\>1.5\*109/L, PLT\>100\*109/L, BIL\<1.5 times of upper limit of normal reference value, ALT and AST\<2.5 times of upper limit of normal reference value, and CRE\<1.2mg/dl
* Good cardiac function before the recruitment, no seizure of myocardial infarction in past half years, and controllable hypertension and other coronary heart disease
* Not concomitant with other uncontrollable benign disease before the recruitment(e.g. the infection in the kidney, lung and liver)
* Not participating in other clinical trials before and during the treatment
* Signed the Informed Consent Form
* No peritoneal metastatic and CY0 in 28 days by laparoscopic exploration
* Non-gastric stump cancer
* No esophagus infiltrating or infiltrating less than 3cm

Exclusion Criteria:

* Distal metastasis to Mediastinal lymph node,liver ,peritoneal,pleural effusion ,ascites,above 16a2-b1 and others
* Severe mental illness
* Her-2 positive, desire for hercptin treatment
* Ever administrated with other drugs(including TCM drugs) before the recruitment, or no guarantee of progress according to the study requirement after recruitment
* Allergy to the drugs in this protocol
* Pregnant and lactating women
* Women at childbearing age and of pregnancy desire during the study

Primary outcomes:
measure: 3 year OS
timeFrame: 3 years
Secondary outcomes:
measure: radical resection rate
timeFrame: 4 months
measure: 3 year DFS
timeFrame: 3 years
measure: 5 year OS
timeFrame: 5 years
measure: adverse events
timeFrame: 7months
Other outcomes:
Locations:
city: Hanzhou
country: China
facility: The first affiliated hospital of zhejiang chinese medical university
state: Zhejiang
Study officials:
affiliation: The First Affiliated Hospital of Zhejiang Chinese Medical University
name: Xiangdong Cheng, MD
role: STUDY_DIRECTOR
References: