Clinical trial NCT02454673: Therapeutic Individualization for Patients With Locally Advanced Gastric and Gastroesophageal Cancer
Official title: Approximation to the Therapeutic Individualization in Patients With Locally Advanced Gastric and Gastroesophageal Cancer Through Modelling and Generation of Predictive Gene Signatures
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Gastric Cancer
Effects of Chemotherapy
Surgery
Keywords: Radiotherapy
Neoadjuvant therapy
Pharmacodynamics
Pharmacokinetics
Nonlinear Dynamics
Lead sponsor: Clinica Universidad de Navarra, Universidad de Navarra
Sponsor class: OTHER
First posted: 2015-05-27
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with locally advanced adenocarcinoma gastric cancer for a neoadjuvant protocol consisting of preoperative chemotherapy or induction chemotherapy, chemoradiotherapy and salvage surgery. Patients must have a medically fit condition to complete the protocol.

Initial staging comprises a thoracic and abdominal computerised tomography scan, endoscopic ultrasound endoscopy (EUS), biopsy and blood test including blood cell count, hepatic and renal function.

Radiological and endoscopic evaluations are performed at baseline and at the completion of chemotherapy and chemoradiotherapy.

Blood tests are acquired at baseline, before each chemotherapy course and concurrently with evaluations. Blood tests are also obtained during follow-up and at the time progression.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival
timeFrame: From date of diagnosis until death, assessed up to 10 years
measure: Disease Free Survival
timeFrame: From date of diagnosis until treatment failure, assessed up to 10 years
Secondary outcomes:
measure: Pathological Response at the Time of Surgery
timeFrame: Weeks 10 to 28
measure: R0 Resection rate at the Time of Surgery
timeFrame: Weeks 10 to 28
measure: Tumor Regression Grade at the Time of Surgery
timeFrame: Weeks 10 to 28
measure: Lymph nodes response at the Time of Surgery
timeFrame: Weeks 10 to 28
measure: Estimate of TN Change From Baseline to Surgery
timeFrame: Weeks 10 to 28
Other outcomes:
Locations:
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
Study officials:
affiliation: Clinica Universidad de Navarra
name: Javier Rodriguez Rodriguez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Moehler M, Baltin CT, Ebert M, Fischbach W, Gockel I, Grenacher L, Holscher AH, Lordick F, Malfertheiner P, Messmann H, Meyer HJ, Palmqvist A, Rocken C, Schuhmacher C, Stahl M, Stuschke M, Vieth M, Wittekind C, Wagner D, Monig 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.
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.