Observational Study of Perioperative Chemotherapy in Gastric Cancer

Gastric Cancer Clinical Trial

— PRECISO  

Official title:

Prospective Observational Study of Patients With Locally Advanced Gastric Cancer Treated With Perioperative Chemotherapy and Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01633203
• Other study ID #: GOCCHI 2009-01
• Status: Completed
• Start date: August 2010
• Est. completion date: December 2018

Study information

• Verified date: March 2019
• Source: Grupo Oncologico Cooperativo Chileno de Investigation
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study will assess the efficacy and toxicity of perioperative chemotherapy with Epirubicin + Cisplatin + Capecitabine (ECX) in routine clinical practice in a network of public hospitals in Santiago, Chile.

Description:

Chile belongs to the countries with a high mortality rate due to gastric cancer, and this disease is the most frequent cause of cancer death in Chile. Despite of adequate surgery, survival rates are disappointing, with less than 60% of patients for all stages achieving to be alive at 5 years. This is due to the fact that frequently gastric cancer is diagnosed at an advanced stage. For locally advanced gastric cancer a multimodality treatment is recommended, with the alternatives of surgery followed by chemotherapy (asian approach), surgery followed by chemoradiation (US approach) and perioperative chemotherapy (european approach). These three strategies are valid standard treatment options and have shown to improve overall survival in stage IB to IVA gastric cancer.

Perioperative chemotherapy administered pre- and postoperatively, has shown to downstage the tumor, increase curative resection, progression free and overall survival.

For patients with potentially resectable gastric cancer staged T2 or higher or cN+, NCCN Guidelines recommend perioperative chemotherapy (category1). Chilean guidelines for gastric cancer state the alternative of perioperative chemotherapy, however this approach has not been used widely in public hospitals because lack of financial support.

Some gastric cancers overexpress HER2, and this subset of patients benefit from targeted therapy at an advanced stage. The proportions of patients with these molecular characteristics vary widely depending of the geographic area. The chilean population has been investigated in small series, but the incidence of HER2 positive gastric cancer is not known. We therefore plan to measure HER2 expression in all participating patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: December 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 80 Years

Eligibility

Inclusion Criteria:

• Histologically proven invasive carcinoma

• Age > 18 years.

• ECOG performance status 0 or 1.

• Hemoglobin > 9 g/dL

• Absolute neutrophil count > 1.5 x 109/L

• Platelet count > 100 x 109/L

• Creatinine < 1.5 ULN

• Creatinine clearance > 60 mL/min

• Serum bilirubin < 1.5 x ULN

• AST < 2.5 x ULN

• Women of child bearing potential: must agree to use an effective contraceptive method.

• Signed informed consent.

Exclusion Criteria:

• ECOG > 2.

• Pre-existing diarrhea uncontrolled with supportive care.

• Inability to swallow Xeloda tablets.

• History of mild-to-moderate renal insufficiency (creatinine clearance < 45 mL/min).

• Signs or symptoms of clinically significant hepatic dysfunction (bilirubin > 1.5 ULN, FA > 2.5 ULN, albumin < 2,5 g/dL).

• Significant cardiac dysfunction (LVEF < LLN)

• Presence of distant metastasis, including clinical signs of peritoneal carcinomatosis

• Symptomatic gastric retention or severe dysphagia with a caloric intake of < 1500 kcal/day

• Histology of lymphoma, GIST or neuroendocrine tumor

• Pregnant or breast-feeding women. Female patients must be postmenopausal, surgically sterile or they must agree to use an effective method of contraception.

• Any medical conditions that, in the investigator's opinion, would impose excessive risk to the patient. Examples of such conditions include congestive heart failure of Class III or IV of the NYHA classification, infection requiring parental or oral treatment, any altered mental status or any psychiatric condition that would interfere with the understanding of the informed consent.

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• epirubicin + cisplatin + capecitabine polychemotherapy
EPIRUBICIN (LKM)at a dose of 50 mg/m2 over 15 minutes is administered every 21 days. CISPLATIN (LKM) at a dose of 60 mg/m2 over 4 hours is administered every 21 days. Patients must receive standardized hydration per protocol. CAPECITABINE (Xeloda®) at a dose of 625 mg/m2 BID (i.e. 1250 mg/m2/day) 30 minutes after meals from day 1 to day 21 of every cycle of chemotherapy. Antiemetic therapy: Dexamethasone 8 mg IV and Ondansetron (LKM) 8 mg IV o Granisetron (Kytril®) prior to chemotherapy Rescue Ondansetron (LKM) 8 mg IV will be given during 24-hour hospitalization in case of emesis Symptomatic antiemetic therapy with thiethylperazine will be prescribed. Loperamide will be prescribed in case of diarrhea.

Locations

Country	Name	City	State
Chile	Instituto Nacional del Cáncer	Santiago	RM

Sponsors (1)

Lead Sponsor	Collaborator
Grupo Oncologico Cooperativo Chileno de Investigation

Country where clinical trial is conducted

Chile, 

References & Publications (3)

Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. — View Citation

García CC, Benavides CC, Apablaza SP, Rubilar PO, Covacevich SR, Peñaloza PM, Guerra JC, Horwitz BZ, Domancic PH, Bustamante R M, Romero S C. [Surgical treatment of gastric cancer: results in 423 cases]. Rev Med Chil. 2007 Jun;135(6):687-95. Epub 2007 Aug 22. Spanish. — View Citation

Okines AF, Norman AR, McCloud P, Kang YK, Cunningham D. Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer. Ann Oncol. 2009 Sep;20(9):1529-34. doi: 10.1093/annonc/mdp047. Epub 2009 May 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of downstaging	To determine the rate of downstaging of locally advanced cT3-4 and/or N+ gastric carcinomas after 3 cycles of preoperative chemotherapy with ECX	through study completion, an average of 3 months
Secondary	Rate of adverse events	Rate and description of adverse events	through study completion, an average of 6 months
Secondary	Clinical response after three cycles of preoperative ECX	Clinical response based on RECIST criteria	through study completion, an average of 6 months
Secondary	To evaluate the surgical morbidity after three cycles of preoperative CT	Hospital stay duration	through study completion, an average of 1 year
Secondary	To evaluate the surgical mortality after three cycles of preoperative CT	30 days postoperative mortality rate	through study completion, an average of 1 year
Secondary	progression free survival	To evaluate the 3 year progression free survival	through study completion, an average of 2 years
Secondary	overall survival	To evaluate the 5 year overall survival (OS) of patients treated with perioperative CT	through study completion, an average of 3 years
Secondary	compliance with the planned postoperative therapy	To evaluate the rate of start and completion of postoperative treatment	through study completion, an average of 1 year
Secondary	EORTC QLQ-C30 after neoadjuvant chemotherapy and surgery	To evaluate quality of life through patient reported outcomes of patients treated with perioperative chemotherapy	through study completion, an average of 2 years
Secondary	EORTC QLQ-STO 22 after neoadjuvant chemotherapy and surgery	To evaluate patient reported specific symptoms of patients treated with perioperative chemotherapy	through study completion, an average of 2 years
Secondary	HER 2 expression	To determine the number of patients with HER2 overexpressing gastric cancers	through study completion, an average of 1 year

External Links

•   Homepage of the Chilean Cooperative Group for Oncological Research