Therapeutic Individualization for Patients With Locally Advanced Gastric and Gastroesophageal Cancer

Gastric Cancer Clinical Trial

Official title:

Approximation to the Therapeutic Individualization in Patients With Locally Advanced Gastric and Gastroesophageal Cancer Through Modelling and Generation of Predictive Gene Signatures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02454673
• Other study ID #: CUN-GCNMEM
• Status: Completed
• Phase: N/A
• First received: May 22, 2015
• Last updated: May 26, 2015
• Start date: September 2013
• Est. completion date: March 2015

Study information

• Verified date: March 2015
• Source: Clinica Universidad de Navarra, Universidad de Navarra
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Comité Ético de Investigación Clínica
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to evaluate whether the R0 rate, pathological response degree, patterns of recurrence and long-term outcomes may be initially predicted in patients with locally advanced gastroesophageal junction and gastric cancer treated with a neoadjuvant approach and salvage surgery.

Description:

Patients with locally advanced gastroesophageal junction and gastric cancer with T3-4 and/or N+ are included. Initially, patients are diagnosed by computerized tomography scan and endoscopic ultrasound. The neoadjuvant strategy consisted of 3-4 cycles of preoperative chemotherapy (group A) or 3-4 courses of induction chemotherapy followed by concurrent chemoradiotherapy (group B). Chemoradiotherapy comprised weekly chemotherapy concurrently with daily external beam radiotherapy up to 45 Gy). Surgery is scheduled 4 to 6 weeks after the end of CRT. Pathological response is graded according to the Becker criteria. Statistical analysis is performed IBM SPSS v20. Nonlinear mixed effects (NLME) modelling is applied to evaluate the impact of dynamic changes in tumor size, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) on the clinical outcome of these patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the stomach or gastroesophageal cancer

• Age =18 years old

• Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1

• Body mass index = 18

• No prior chemotherapy or chemoradiotherapy

• TNM stage of T3-T4 and/or positive regional lymph nodes (N+) by endoscopic ultrasound or computed tomography (CT)

• No evidence of metastasis (M0)

• Adequate hematological, liver and renal functions (ALT and AST=2.5 UNL, total bilirubin =1.5 UNL, and serum creatinine =1.5 UNL)

Exclusion Criteria:

• Patients with previous (less than 10 years) or current history of malignant neoplasms, except for curatively treated

• Patients with evidence of severe or uncontrolled systemic disease

• Medically unfit for chemotherapy

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Effects of Chemotherapy
• Gastric Cancer
• Surgery

Locations

Country	Name	City	State
Spain	Clinica Universidad de Navarra	Pamplona	Navarra

Sponsors (1)

Lead Sponsor	Collaborator
Clinica Universidad de Navarra, Universidad de Navarra

Country where clinical trial is conducted

Spain, 

References & Publications (6)

Carton E, Caldwell MT, McDonald G, Rama D, Tanner WA, Reynolds JV. Specialized intestinal metaplasia in patients with gastro-oesophageal reflux disease. Br J Surg. 2000 Jan;87(1):116-21. — View 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. — View Citation

Lee S, Oh SY, Kim SH, Lee JH, Kim MC, Kim KH, Kim HJ. Prognostic significance of neutrophil lymphocyte ratio and platelet lymphocyte ratio in advanced gastric cancer patients treated with FOLFOX chemotherapy. BMC Cancer. 2013 Jul 22;13:350. doi: 10.1186/1471-2407-13-350. — View Citation

Moehler M, Baltin CT, Ebert M, Fischbach W, Gockel I, Grenacher L, Hölscher AH, Lordick F, Malfertheiner P, Messmann H, Meyer HJ, Palmqvist A, Röcken C, Schuhmacher C, Stahl M, Stuschke M, Vieth M, Wittekind C, Wagner D, Mönig SP. International comparison of the German evidence-based S3-guidelines on the diagnosis and multimodal treatment of early and locally advanced gastric cancer, including adenocarcinoma of the lower esophagus. Gastric Cancer. 2015 Jul;18(3):550-63. doi: 10.1007/s10120-014-0403-x. Epub 2014 Sep 7. — View Citation

Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. doi: 10.1200/JCO.2008.17.0506. Epub 2009 Jan 12. — View Citation

Xiong BH, Cheng Y, Ma L, Zhang CQ. An updated meta-analysis of randomized controlled trial assessing the effect of neoadjuvant chemotherapy in advanced gastric cancer. Cancer Invest. 2014 Jul;32(6):272-84. doi: 10.3109/07357907.2014.911877. Epub 2014 May 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Overall survival was defined as the period from diagnosis until death (from any cause). Nonlinear mixed effects population modelling to evaluate the impact in clinical outcome of dynamic markers as tumor size, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR).	From date of diagnosis until death, assessed up to 10 years	No
Primary	Disease Free Survival	DFS was defined as the time from diagnosis to the first date of local or distant cancer. Nonlinear mixed effects population modelling to evaluate the impact in clinical outcome of dynamic markers as tumor size, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR).	From date of diagnosis until treatment failure, assessed up to 10 years	No
Secondary	Pathological Response at the Time of Surgery	Specimen analysis according to TNM classification. Pathological complete response is defined as no invasive cancer cells in the surgical specimen.	Weeks 10 to 28	No
Secondary	R0 Resection rate at the Time of Surgery	The R0 resection rate after the neoadjuvant protocol. R0 is defined as a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.	Weeks 10 to 28	No
Secondary	Tumor Regression Grade at the Time of Surgery	Estimate of tumor regression grade at the time of surgery according to Becker Criteria: Grade 1a, No residual tumor; Grade 1b, <10% residual tumor; Grade 2, 10-50% residual tumor; Grade 3, >50% residual tumor.	Weeks 10 to 28	No
Secondary	Lymph nodes response at the Time of Surgery	Participants were assessed for node-negative lymph nodes at the time of surgery according to TNM classification. Node-negative (pN0) participants had no regional lymph node metastasis.	Weeks 10 to 28	No
Secondary	Estimate of TN Change From Baseline to Surgery	Estimate of TN change due to neoadjuvant treatment is defined as the estimate of the evidence of downstaging between baseline and surgery	Weeks 10 to 28	No