Clinical trial NCT01633203: Observational Study of Perioperative Chemotherapy in Gastric Cancer
Official title: Prospective Observational Study of Patients With Locally Advanced Gastric Cancer Treated With Perioperative Chemotherapy and Surgery
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Gastric Cancer
Keywords: gastric cancer
combination chemotherapy
HER-2 gene
quality of life
Lead sponsor: Grupo Oncologico Cooperativo Chileno de Investigation
Sponsor class: NETWORK
First posted: 2012-07-04
Enrollment: 61
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Current diagnosis of T3-4 and/or N+ M0 (according to staging system of the American Joint Committee on Cancer 2002) resectable gastric cancer. The resectability has to be confirmed by a surgical oncologist and/or Oncological Committee.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of downstaging
timeFrame: through study completion, an average of 3 months
Secondary outcomes:
measure: Rate of adverse events
timeFrame: through study completion, an average of 6 months
measure: Clinical response after three cycles of preoperative ECX
timeFrame: through study completion, an average of 6 months
measure: To evaluate the surgical morbidity after three cycles of preoperative CT
timeFrame: through study completion, an average of 1 year
measure: To evaluate the surgical mortality after three cycles of preoperative CT
timeFrame: through study completion, an average of 1 year
measure: progression free survival
timeFrame: through study completion, an average of 2 years
measure: overall survival
timeFrame: through study completion, an average of 3 years
measure: compliance with the planned postoperative therapy
timeFrame: through study completion, an average of 1 year
measure: EORTC QLQ-C30 after neoadjuvant chemotherapy and surgery
timeFrame: through study completion, an average of 2 years
measure: EORTC QLQ-STO 22 after neoadjuvant chemotherapy and surgery
timeFrame: through study completion, an average of 2 years
measure: HER 2 expression
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Instituto Nacional del Cáncer
state: RM
Study officials:
affiliation: Grupo Oncologico Cooperativo Chileno de Investigation
name: Bettina G Muller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1056/NEJMoa055531.
citation: Okines AFC, 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):1529-1534. doi: 10.1093/annonc/mdp047. Epub 2009 May 27.
citation: Garcia CC, Benavides CC, Apablaza SP, Rubilar PO, Covacevich SR, Penaloza 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.