Phase II Multicenter Randomized Trial of Neoadjuvant Chemotherapy and Chemoradiotherapy Regimens in Resectable Gastric Adenocarcinoma: Docetaxel, Capecitabine, Paclitaxel, Oxaliplatin, Carboplatin

The primary objective of this study is to evaluate which **preoperative regimen** provides superior event-free survival one year after randomization in patients with resectable gastric cancer. This is clinically relevant as it aims to identify the most effective treatment strategy to improve patient outcomes in terms of survival without disease progression.

Secondary objectives include:

• Assessing the time to event of all treatment arms.
• Determining which preoperative regimen offers superior time-to-recurrence (TTR).
• Evaluating the feasibility of preoperative regimens based on toxicity, pathological complete response (pCR), and R0 resection rates.
• Assessing the toxicity profile of all treatment arms.
• Documenting surgical morbidity, including the incidence of anastomotic leakage.
• Determining the pCR rates of all treatment arms.
• Determining the R0 resection rates of all treatment arms.
• Determining the response rate (RR) of all treatment arms.
• Determining the overall survival (OS) of all treatment arms.
• Identifying which preoperative regimen (CRITICS-II) will be compared with the new standard treatment (CRITICS-I) in a subsequent phase III trial.

The clinical trial involves participants diagnosed with **gastric adenocarcinoma** at TNM 8th edition stages IB to IIC. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a resectable adenocarcinoma of the stomach or gastro-oesophageal junction, with no prior abdominal radiotherapy. The trial does not include a vulnerable population. Participants must maintain a caloric intake of at least 1500 kcal per day, verified by a dietician, and meet specific hematological, renal, and liver function criteria. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the efficacy of different preoperative regimens in patients with resectable **gastric cancer**. This is a multicenter, randomized, phase II trial comparing three treatment arms: neo-adjuvant chemotherapy followed by surgery, neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery, and neo-adjuvant chemoradiotherapy followed by surgery. The primary objective is to determine which regimen provides superior event-free survival one year after randomization. The trial is expected to run from November 2017 to July 2028, with participants involved for a maximum treatment period of up to 12 months, depending on the assigned regimen.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically proven TNM 8th edition stage IB-IIC gastric adenocarcinoma, adequate caloric intake, and specific hematological and renal function parameters. Following randomization, treatment will commence within 15 working days. Regular follow-up visits will be scheduled to monitor treatment response and manage any adverse events. The end-of-study visit will assess the primary endpoint of event-free survival, defined as the absence of local, regional, or distant recurrence, progression, or death from any cause.

Participants may be withdrawn from the study if they experience significant adverse effects, fail to comply with the study protocol, or if the investigator deems it in the participant's best interest. The trial employs a double-blind, controlled design to ensure unbiased results. The investigational products include **docetaxel**, **capecitabine**, **paclitaxel**, **oxaliplatin**, and **carboplatin**, administered via intravenous infusion or orally, depending on the specific regimen. The trial's rigorous methodology and comprehensive design aim to provide valuable insights into optimizing preoperative treatment strategies for gastric cancer.

The clinical trial involves the administration of several **cytostatic** agents, each with specific dosing regimens and routes of administration. **Docetaxel** is administered as an intravenous infusion with a maximum daily dose of 50 mg/m². The treatment period for docetaxel is up to 12 weeks. This agent is utilized in its chemical form and is not a pediatric formulation.

**Capecitabine** is administered orally with a maximum daily dose of 850 mg/m². The treatment duration for capecitabine is up to 11 weeks. Like the other agents in this trial, capecitabine is a chemical substance and is not formulated for pediatric use.

**Paclitaxel** is delivered via intravenous infusion, with a maximum daily dose of 50 mg/m². The treatment period for paclitaxel is up to 5 weeks. This agent is also a chemical substance and is not intended for pediatric patients.

**Oxaliplatin** is administered through intravenous infusion, with a maximum daily dose of 100 mg/m². The treatment duration for oxaliplatin is up to 12 weeks. It is a chemical substance and is not a pediatric formulation.

**Carboplatin** is given as an intravenous infusion with a maximum daily dose of 2 units, with a treatment period of up to 5 weeks. This agent is also a chemical substance and is not formulated for pediatric use.

All medications in this trial are classified as cytostatic agents and are used in their chemical forms. The trial does not involve any pediatric formulations or orphan drug designations. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.

The efficacy of the clinical trial will be assessed primarily through the evaluation of **event-free survival** at 1 year after randomization. This primary endpoint will consider events such as local recurrence, regional recurrence, local-regional recurrence or progression, distant recurrence, or death from any cause. The trial aims to determine which preoperative regimen provides superior event-free survival in patients with resectable gastric cancer. The assessment will involve a comparison of different preoperative modalities, including systemic therapy (chemotherapy), locoregional therapy (chemoradiotherapy), and a combination of both, to ascertain their contribution to therapeutic efficacy.