Neoadjuvant TACiE in Locally Advanced Gastric Cancer

Study Overview
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Brief Summary
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This is a prospective, single-center, single-arm, phase 2 trial to evaluate the feasibility and safety of neoadjuvant transcatheter infusion and embolism (TACiE) in patients with locally advanced adenocarcinoma of stomach and gastroesophageal junction. The TACiE protocol includes four cycles. Transcatheter oxaliplatin and concurrent embolism on day 1 and oral S-1 on day 1-14 will be administrated in the first and third cycles. Intra-venous oxaliplatin on day 1 and oral S-1 on day 1-14 (SOX) will be administrated in the second and fourth cycles.

Detailed Description
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The treatment of advanced gastric cancer has been a significant global health problem. With surgery still the backbone, many clinical trials have shown the benefit of perioperative treatment to gastric cancer patients. The neoadjuvant treatment is one of the most important parts. Besides chemotherapy and chemoradiotherapy, the report of transcatheter arterial infusion (TAI) or transcatheter arterial embolism (TAE) in gastric cancer is relatively limited, though some case reports have showed its efficacy and safety in advanced gastric cancer. The combination of TAI and TAE (TACiE) may be more perspective in the treatment of gastric cancer. With transarterial infusion chemotherapy, TACiE increases the local concentration of chemotherapeutic agents and reduces adverse reaction. With embolization, TACiE blocks the blood supply and causes the necrosis of tumors, in this way exposing tumor antigen and promoting tumor immunity. Based on those knowledges, we designed this prospective, single-center, single-arm, phase 2 trial to evaluate the feasibility and safety of neoadjuvant transcatheter infusion and embolism (TACiE) in patients with locally advanced adenocarcinoma of stomach and gastroesophageal junction. The primary purpose of this study is to evaluate the pathologic complete response (pCR) rate of TACiE. The second purpose is to evaluate pathologic response rate (pRR), objective Response Rate (ORR), overall survival (OS) and progression-free survival (PFS) of the patients enrolled in this study.

Official Title
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Neoadjuvant Transcatheter Arterial Chemoinfusion and Embolism (TACiE) for Patients With Locally Advanced Adenocarcinoma of Stomach and Gastroesophageal Junction: a Prospective, Phase 2, Single Arm Trial.

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Oxaliplatin
* Drug: Teysuno
* Procedure: Transarterial chemoembolization (TACE)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18 to 75 years old; The Karnofsky Performance Scale (KPS) score >=80; Adenocarcinoma of stomach and gastroesophageal junction (Siewert II/III) diagnosed pathologically; clinical T3-4a/N+/M0 (The 8th edition of the American Joint Committee on Cancer (AJCC) staging system); According to the Response Evaluation Criteria In Solid Tumours (RECIST) 1.1 standard, there is at least one evaluable lesion in the abdominal CT/MRI; The surgeons participating in this study judged the lesion to be resectable; Physical condition allows the surgery; Exclusion Criteria: Distant metastasis or local unresectable factors; Cytotoxic chemotherapy, radiotherapy, immunotherapy or radical surgery for the treatment of this gastric cancer, except for corticosteroids; Active autoimmune diseases or a history of autoimmune diseases; History of malignant tumors within 2 years; Gastrointestinal bleeding within two weeks prior to enrollment, or those with high bleeding risk; Gastrointestinal perforation and/or fistula occurred within 6 months before enrollment; Upper gastrointestinal obstruction or abnormal physiological function or suffering from malabsorption syndrome, which may affect the absorption of drugs; Weight loss >=20% within 2 months before enrollment; A history of the following lung diseases: interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis, acute lung disease, etc.; Uncontrollable systemic diseases including diabetes, hypertension, etc.; Severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis, HIV infection, etc.; Untreated patients with chronic hepatitis B or chronic HBV carriers with hepatitis B virus (HBV) DNA exceeding 500 IU/mL, or hepatitis C virus (HCV) RNA positive patients should be excluded; Any of the following cardiovascular risk factors (refer to Research Guide); Known peripheral nerve disease >=NCI CTCAE Grade 1. However, patients with only the disappearance of the deep tendon reflex (DTR) need not be excluded; Moderate or severe renal damage [creatinine clearance equal to or lower than 50 ml/min (calculated according to the Cockcroft and Gault equation)], or serum creatinine> upper limit of normal (ULN); People with known dihydropyrimidine dehydrogenase (DPD) deficiency; Those who are allergic to any research drug ingredients; Underwent major surgery within 28 days prior to enrollment;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SOX-TACiE<br>Preoperative transcatheter arterial chemoinfusion and embolism alternated with intra-venus chemotherapy. | Drug: Oxaliplatin<br>* The first and third cycles : transcatheter arterial infusion of oxaliplatin 85mg/m2, day 1. The second and fourth cycles: intra-venous oxaliplatin 135mg/m2, day 1.<br>Drug: Teysuno<br>* Oral S-1, 40mg-60mg, day 1-14 for four 21-day cycles.<br>Procedure: Transarterial chemoembolization (TACE)<br>* In the first and third cycles : transcatheter arterial infusion of oxaliplatin 85mg/m2, day 1; transcatheter arterial embolism of tumor feeding arteries, day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response (pCR) rate | The percentage of patients found no tumor residual in primary tumor and resected lymph nodes. | two weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate (pRR) | The percentage of patients found less than 10% tumor residual in primary tumor. | two weeks after surgery | 
| Objective response rate (ORR) | The percentage of patients found complete response or partial response to preoperative therapy according to RECIST v1.1. | up to 3 months | 
| The incidence of treatment emergent adverse events. | Safety | up to 1 month after surgery. | 
| Overall survival | The time from enrollment to death caused by any causes or censor. | From date of enrollment until the date of death from any cause, assessed up to 36 months | 
| Progressive free survival | The time from enrollment to tumor progression, death or censor. | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neoadjuvant therapy, transcatheter arterial infusion, transcatheter arterial embolism, SOX