Phase II Study of Avelumab Plus Chemotherapy in the Peri-operative Treatment for Patients With Resectable Gastric Cancer (GC) or Gastroesophageal Junction Cancer (GEJC)

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Phase II Study of Avelumab plus chemotherapy in the peri-operative treatment for patients with resectable Gastric cancer (GC) or Gastroesphageal Junction cancer (GEJC) The addition of Avelumab to the perioperative chemotherapy in GC and GEJC patients may increase pathological responses by a synergic...

Phase II Study of Avelumab plus chemotherapy in the peri-operative treatment for patients with resectable Gastric cancer (GC) or Gastroesphageal Junction cancer (GEJC) The addition of Avelumab to the perioperative chemotherapy in GC and GEJC patients may increase pathological responses by a synergic effect activating the immune response. Conclusively, the survival of these patients would improve. The primary objective is to investigate whether the addition of avelumab to FLOT chemotherapy (docetaxel, oxaliplatin and fluorouracil/leucovorin) improves efficacy in terms of pathological complete response (pCR) rate, in GC and GEJC patients compared to the historical data of chemotherapy alone in the neoadjuvant setting. Secondary objectives are as follows: To evaluate the addition of avelumab to the perioperative chemotherapy in regard to the following: Overall survival (OS) Disease-free survival (DFS) Progression-free survival (PFS) Surgical resection rate (R0) Overall Response Rate (ORR) to neoadjuvancy To determine the safety and tolerability of avelumab with FLOT chemotherapy. To perform a comprehensive analysis of biomarkers, as exploratory endpoints. Study design: This is an open-label, non-randomized, multicentric phase II clinical trial in subjects with operable gastric or GEJ adenocarcinoma. Tissue biopsies before and after treatment will be required. Blood samples will be required at different points of the treatment for biomarker analyses. Tumor imaging assessments will be performed at baseline, after the neoadjuvant treatment, and after finalizing the adjuvancy with avelumab/FLOT, and every 6 months thereafter to determine response to treatment. Clinical decision making will be based on Investigator assessment of the scans using RECIST v1.1. Safety of avelumab/FLOT will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported. Study population: Patients with resectable gastric and GEJ cancer suitable for preoperative chemotherapy. Statistical Considerations: Summary tables (descriptive statistics and frequency tables) will be provided for all demographic, baseline and safety variables, as appropriate. Continuous variables will be summarized with descriptive statistics (mean, standard deviation, range, and median). Ninety-five (95) percent confidence intervals (95% CI) may also be presented, as appropriate. Frequency counts and percentage of subjects within each category will be provided for categorical data. The primary efficacy analysis (pCR) will be performed using the binomial test procedure. Additionally, for the pCR rate one-sided 90% CI will be also presented to be consistent with sample size calculation. Secondary endpoints will be summarized with descriptive statistics. Survival analysis will be performed to analyse OS, PFS and DFS. Kaplan- Meier curves will be presented and possible comparisons will be tested using the log-rank test or the Cox proportional hazard model for multivariate analysis, hazard ratios (HR) and their 95% confidence interval (CI95%) will be provided. Any survival analyses will be considered as exploratory. The study population are patients with resectable gastric and GEJ cancer suitable for preoperative chemotherapy. The study duration will be approximately 24 months of recruitment; 5 years of additional followup. Regarding to the study product, peri-operatory treatment consisting of four cycles (each cycle is 14 days) of neoadjuvant chemotherapy (docetaxel, oxaliplatin and fluorouracil/leucovorin) plus avelumab previous to surgery. Surgery is recommended to be scheduled 4 to 6 weeks after the last dose. Afterwards (4 to 10 weeks after surgery), four cycles of adjuvant therapy with the same schema, followed by avelumab up to one year. Finally, this study will be conducted in 10 centres in Spain.

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