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

Primary Purpose

Stomach Neoplasm, GastroEsophageal Cancer, Adenocarcinoma

Status

Recruiting

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

Tegafur-Gimeracil-Oteracil Potassium

Chemoradiotherapy

Gastric resection

Oxaliplatin

About this trial

This is an interventional treatment trial for Stomach Neoplasm focused on measuring Randomized, Open Label, Multicenter

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Fudan University Shanghai Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Preoperative radiochemotherapy

Preoperative chemotherapy

Arm Description

1 cycle preoperative chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin. 5 weeks preoperative chemoradiotherapy. 1 cycle preoperative chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin. Gastric resection. 3 cycles adjuvant chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin.

3 cycles preoperative chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin. Gastric resection. 3 cycles adjuvant chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin.

Outcomes

Primary Outcome Measures

Disease free survival

Secondary Outcome Measures

Overall survival

Surgical complete resection rate (R0)

Pathological response rate

Proportion of patients with toxicities

Proportion of patients with surgery-related complication

Full Information

NCT ID

NCT03013010

First Posted

January 4, 2017

Last Updated

July 2, 2020

Sponsor

Shanghai Cancer Hospital, China

Collaborators

Fudan University, Ruijin Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Huadong Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03013010

Brief Title

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

Acronym

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)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Recruiting

Study Start Date

December 2016 (undefined)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shanghai Cancer Hospital, China

Collaborators

Fudan University, Ruijin Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Huadong Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stomach Neoplasm, GastroEsophageal Cancer, Adenocarcinoma, Locally Advanced Cancer, Chemoradiation

Keywords

Randomized, Open Label, Multicenter

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

682 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Preoperative radiochemotherapy

Arm Type

Experimental

Arm Description

Arm Title

Preoperative chemotherapy

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tegafur-Gimeracil-Oteracil Potassium

Other Intervention Name(s)

S-1

Intervention Description

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.

Intervention Type

Radiation

Intervention Name(s)

Chemoradiotherapy

Other Intervention Name(s)

radiochemotherapy

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Gastric resection

Other Intervention Name(s)

Gastrectomy

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin

Intervention Description

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

Primary Outcome Measure Information:

Title

Disease free survival

Time Frame

up to 3 years

Secondary Outcome Measure Information:

Title

Overall survival

Time Frame

up to 3 years

Title

Surgical complete resection rate (R0)

Time Frame

at the time of surgery

Title

Pathological response rate

Time Frame

at the time of surgery

Title

Proportion of patients with toxicities

Time Frame

up to 3 years

Title

Proportion of patients with surgery-related complication

Time Frame

at the time of surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zhen Zhang, M.D.

Phone

(86)13661738625

Zhenzhang6@gmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Xiao-wen Liu, M.D.

Phone

(86)13636698200

liuxw1129@hotmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ya-nong Wang, M.D.

Organizational Affiliation

Fudan University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Zhen Zhang, M.D.

Organizational Affiliation

Fudan University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fudan University Shanghai Cancer Center

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200032

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhen Zhang, M.D.

Phone

(86)13661738625

zhenzhang6@gmail.com

First Name & Middle Initial & Last Name & Degree

Xiaowen Liu, M.D.

Phone

(86)13636698200

liuxw1129@hotmail.com

12. IPD Sharing Statement

Plan to Share IPD

Yes

Citations:

PubMed Identifier

31221115

Citation

Liu X, Jin J, Cai H, Huang H, Zhao G, Zhou Y, Wu J, Du C, Long Z, Fang Y, Ma M, Li G, Zhou M, Yin J, Zhu X, Zhu J, Sheng W, Huang D, Zhu H, Zhang Z, Lu Q, Xie L, Zhang Z, Wang Y. Study protocol of a randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma: PREACT. BMC Cancer. 2019 Jun 20;19(1):606. doi: 10.1186/s12885-019-5728-8.

Results Reference

derived

PubMed Identifier

30373600

Citation

Liu X, Cai H, Sheng W, Huang H, Long Z, Wang Y. microRNAs expression profile related with response to preoperative radiochemotherapy in patients with locally advanced gastric cancer. BMC Cancer. 2018 Oct 29;18(1):1048. doi: 10.1186/s12885-018-4967-4.

Results Reference

derived

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

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