PREACT Study: Locally Advanced Gastric Cancer, Chemoradiotherapy vs. Chemotherapy Followed by D2 Surgery and Adjuvant Chemotherapy

Adenocarcinoma Clinical Trial

— PREACT  

Official title:

A Randomized, Controlled, Multicenter Study to Compare Preoperative Radiochemotherapy With Preoperative Chemotherapy in Patients With Locally Advanced Gastric or Esophagogastric Junction Adenocarcinoma (PREACT Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03013010
• Other study ID #: FUSCC-LAGCCS002
• Status: Recruiting
• Phase: Phase 3
• Start date: December 2016
• Est. completion date: December 2023

Study information

• Verified date: July 2020
• Source: Shanghai Cancer Hospital, China
• Contact: Zhen Zhang, M.D.
• Phone: (86)13661738625
• Email: Zhenzhang6[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Although the incidence of gastric cancer has been substantially declining for several decades, it is still the sixth most common cancer and the fourth most frequent cause of cancer death worldwide. Surgery is still the only curative option for gastric cancer. However, most patients are unable to undergo surgery because of late stage, unresectable disease. The prognosis for these patients is very poor. Although the Magic trial showed that perioperative chemotherapy can increase the rate of curative surgery and significantly improve overall survival in patients with operable gastric or lower esophageal adenocarcinomas, no pCR events were reported in this trial. The intervention arm in PREACT consists of pre-operative chemotherapy, pre-operative radiochemotherapy, surgery and post-operative chemotherapy. The control arm consists of pre-operative chemotherapy, surgery, and post-operative chemotherapy. The primary purpose of PREACT is to investigate whether the addition of radiochemotherapy to chemotherapy is superior to chemotherapy alone in the pre-operative setting in improving disease free survival in patients with locally advanced gastric or esophagogastric junction adenocarcinoma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 682
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >=18 years

• Female and male

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Life expectancy >=6 months

• Histologically proven adenocarcinoma of the stomach or gastroesophageal junction (GEJ) (excluding Siewert I) that is: Stage IIB (T3N1 only), IIIA (T2N3 not eligible), IIIB, and IIIC, i.e. T3 - T4a and node positive, or T4b and/ or node positive, according to American Joint Committee on Cancer (AJCC) 7th edition

• Considered operable following initial staging investigations or after pre-operative therapy Disease which can be radically treated with radiotherapy to 45 Gy with standard fractionation

• Adequate organ function defined as follows:

• Bone marrow: Haemoglobin >=90 g/L, Absolute neutrophil count (ANC) >=1.5 x 109 /L, Platelet count >=100 x 109 /L; Hepatic: Serum bilirubin <=1.5 x upper limit of normal, aspartate aminotransferase (AST) and/or alanine transaminase (ALT) <=2.5 x upper limit of normal; Renal: Serum creatinine <=1.0 x upper limit of normal

• Patients are willing to obey the treatment and provide blood and tissue specimens

• Written informed consent obtained before randomization

Exclusion Criteria:

• Pregnant or lactating females or female patients of childbearing potential who have not been surgically sterilized or are without adequate contraceptive measures

• Sexually active males or females refuse to practice contraception during the study until 30 days after end of study

• Evidence of metastatic disease

• Prior chemotherapy or radiotherapy

• Patients with a past history of cancer in the 5 years before randomization except for the squamous or basal cell carcinoma of the skin that has been effectively treated, and carcinoma in situ of the cervix that has been treated by operation

• Patients with other significant underlying medical conditions that may be aggravated by the study treatment or are not controlled

• Patients with central nervous system(CNS) disorder or peripheral nervous system disorder or psychiatric disease

• Known history of uncontrolled or symptomatic angina, uncontrolled arrhythmias and hypertension, or congestive heart failure, or cardiac infarction within 6 months prior to study enrollment, or cardiac insufficiency

• Concurrent severe infection

• Severe gastrointestinal bleeding, gastrointestinal perforation

• Unable to swallow

• Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety

• Known hypersensitivity reaction or metabolic disorder to S-1or oxaliplatin

• Renal impairment (GFR <=50ml/min)

• Linitis plastica

Related Conditions & MeSH terms

• Adenocarcinoma
• Chemoradiation
• GastroEsophageal Cancer
• Locally Advanced Cancer
• Stomach Neoplasm
• Stomach Neoplasms

Intervention

Drug:
• Tegafur-Gimeracil-Oteracil Potassium
The dose of S-1 is according to body-surface area (BSA): patients with a BSA of less than 1.25 m2 received 80 mg daily; those with a BSA of 1.25 m2 or more but less than 1.5 m2 received 100 mg daily; and those with a BSA of 1.5 m2 or more received 120 mg daily. oxaliplatin 130mg/m2, intravenously, on day 1.

Radiation:
• Chemoradiotherapy
Chemotherapy: S-1 40-60mg/m2 orally, oral tablet twice daily, days 1-5 of each week of radiotherapy. Radiotherapy: 45 Gy of radiation in 25 fractions, five days per week for five weeks.

Procedure:
• Gastric resection
A standard D2 gastrectomy was recommended. The type of gastrectomy performed depended on the location and extent of the primary lesion. For middle third tumors, the gastric margin was recommended to be more than 5 cm, and a total gastrectomy was performed. For lower third tumors, a 2 cm duodenal margin was recommended and a subtotal or total gastrectomy was considered. For upper third tumors, a 3 cm esophageal margin was recommended and a total gastrectomy or esophagogastrectomy was performed. Billroth I or Roux-en-y gastrojejunostomy was performed for distal gastrectomy patients, Roux-en-y esophagojejunostomy was performed for total gastrectomy patients.

Drug:
• Oxaliplatin
The dose of oxaliplatin is according to body-surface area (BSA): 130mg/m2, intravenously, on day 1.

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (6)

Lead Sponsor	Collaborator
Shanghai Cancer Hospital, China	Fudan University, Huadong Hospital, Ruijin Hospital, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease free survival		up to 3 years
Secondary	Overall survival		up to 3 years
Secondary	Surgical complete resection rate (R0)		at the time of surgery
Secondary	Pathological response rate		at the time of surgery
Secondary	Proportion of patients with toxicities		up to 3 years
Secondary	Proportion of patients with surgery-related complication		at the time of surgery