A Feasibility Study for Convernsion Therapy Using S1/Paclitaxel Chemotherapy Plus Apatinib in ELM Gastric Cancer

Phase II Study of Convernsion Therapy Using S1/Paclitaxel Chemotherapy Plus Apatinib in ELM Gastric Cancer

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.

Study Overview

• Status: Unknown
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: SPA

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hanzhou, Zhejiang, China, 310006
      • The First Affiliated Hospital of Zhejiang Chinese Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conversion treatment; after 3-4 cycles S1/Paclitaxel chemotherapy plus Apatinib,subsequent surgery will be conducted with curative intent.	Drug: SPA; S1/Paclitaxel chemotherapy plus Apatinib S1:60mg twice daily(after the breakfast and supper) for two weeks, and then suspend for one week Paclitaxel:150mg/m2,iv, 3h, at day1 Apatinib:425mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 year OS	The overall survival time	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
radical resection rate	the radical resection rates	4 months
3 year DFS	the diesease free survival time	3 years
5 year OS	The overall survival time	5 years
adverse events	number and degree of adverse events	7months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhejiang Chinese Medical University
• Collaborators: Zhejiang Cancer Hospital; Fujian Cancer Hospital
• Investigators: Study Director: Xiangdong Cheng, MD, The First Affiliated Hospital of Zhejiang Chinese Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): August 24, 2017
• Primary Completion (Anticipated): August 22, 2020
• Study Completion (Anticipated): October 22, 2021

Study Registration Dates

• First Submitted: August 20, 2017
• First Submitted That Met QC Criteria: August 21, 2017
• First Posted (Actual): August 22, 2017

Study Record Updates

• Last Update Posted (Actual): August 22, 2017
• Last Update Submitted That Met QC Criteria: August 21, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Conversion therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: Ahead-G328

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No