Back to resultsConcurrent Neoadjuvant Chemoradiotherapy Plus Trastuzumab in the Treatment of Siewert II ，III of Human Epidermal Growth Factor Receptor-2(HER-2) Positive Gastroesophageal Junction Adenocarcinoma： A Randomized, Controlled Clinical Study
Primary Purpose
Gastroesophageal Junction Adenocarcinoma
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Trastuzumab
Capecitabine
Oxaliplatin
Radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Gastroesophageal Junction Adenocarcinoma
Eligibility Criteria
Inclusion Criteria:
- Age:18 to 60 years old (man or female);
- confirmed to Siewert II , III of locally advanced adenocarcinoma at gastroesophageal junction. The her-2 positive was detected by immunohistochemistry or Fluorescence in SituHybridization(FISH);
- Patients with Stage for Ⅲ by Endorectal Ultrasonography( EUS), Computed Tomography(CT) (or Positron Emission Tomography(PET )-CT) and laparoscopic (According to the eighth edition of American Joint Committee on Cancer (AJCC) );
- Patients are diagnosed as potentially resectable by multidisciplinary team, no surgical contraindications, and expected to be surgical resection;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
- Major organ function has to meet the following criteria:
HB≥80g/L; ANC≥1.5×109/L; PLT≥90×109/L; Alanine Transaminase (ALT) and Aspartate Transaminase(AST)≤2.5×ULN, but<≤5×ULN if the transferase elevation is due to liver metastases； Total Bilirubin(TBIL)<1.5×ULN； Serum creatinine ≤1.5×ULN;Serum albumin ≥ 30g / L
- Life expectancy greater than or equal to 6 months;
- Participants were willing to join in this study, and written informed consent, good adherence, cooperate with the follow-up.
Exclusion Criteria:
- Allergic to trastuzumab, capecitabine and oxaliplatin;
- severe diseases such as liver and kidney，myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia，which affect the situation of chemotherapy or surgery
- A variety of factors influencing oral drugs (such as unable to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction, etc);
- Patients with tendency of gastrointestinal bleeding, including the following: a local active ulcerative lesions, and defecate occult blood (+ +); Has melena and hematemesis in two months;
- Coagulant function abnormality (International Normalized Ratio(INR) > 1.5 ULN, Activated Partial Thromboplastin Time(APTT ) > 1.5 ULN), with bleeding tendency;
- Pregnant or lactating women;
- Patients with other malignant tumors within 5 years (except for curable skin basal cell carcinoma and cervical carcinoma in situ);
- History of psychiatric drugs abuse and can't quit or patients with mental disorders;
- Less than 4 weeks from the last clinical trial;
- The researchers think inappropriate.
Sites / Locations
- Fourth Affiliated Hospital of Hebei Medical University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Trastuzumab XELOX and radiotherapy
XELOX and radiotherapy
Arm Description
Trastuzumab is intravenously administered with the loading dose of 8 mg/kg followed by maintenance dose of 6mg/kg in day 1 of each cycle. XELOX：Capecitabine 825~1000mg/m2 bid d1-14，Oxaliplatin 130 mg/m2 Ivgtt d1 q3w Radiotherapy：45 Gray (unit)Gy/25f （1.8Gy/f/d，5 f/w）
Capecitabine：825~1000mg/m2 bid d1-14，Oxaliplatin 130 mg/m2 Ivgtt d1 q3w Radiotherapy：45Gy/25f （1.8Gy/f/d，5 f/w）
Outcomes
Primary Outcome Measures
The pathological complete response rate(pCR)
The lesion disappeared completely by pathology
Secondary Outcome Measures
Overall survival (OS)
Baseline to measured date of death from any cause
Disease-free survival(DFS)
Baseline to measured date of recurrence or death from any cause
Disease Control Rate (DCR)
Percentage of participants who achieved a best overall response of CR or PR or Stable Disease (SD).
Percentage of Participants With Objective Response According to Modified Response Evaluation Criteria In Solid Tumors(mRECIST) v1.1
Objective response referred to participants with complete response (CR) or partial response (PR). CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: greater than or equal to (>=) 30% decrease in sum of the longest diameter (LD) of all target lesions taking as reference the screening sum LD. To be assigned a status of PR or CR, changes in tumor measurements had to be confirmed by repeat assessments that should have been performed no less than 4 weeks after the criteria for response were first met. Longer intervals as determined by the study protocol were also appropriate. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.
Percentage of Participants With Clinically Significant Improvement in European Organisation for Research and Treatment of Cancer Quality of Life Core Module 30 (EORTC Quality of Life Questionnaire (QLQ)-C30) Score
The EORTC QLQ-C30 is a validated, cancer-specific 30-item patient-reported measure, and contains 14 domains to assess the impact of cancer treatment on 5 aspects of participants functioning (physical, role, cognitive, emotional, and social), 9 aspects of disease/treatment-related symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, loss of appetite, constipation, diarrhea) and a global QoL/overall health status scale. Questions used 4 point scale (1 'Not at all' to 4 'Very much'; with the exception of the QoL/health status scale which uses a 7-point scale (1 'very poor' to 7 'Excellent'). Each scale is transformed on a scale of 0-100; a higher score equals (=) a better level of functioning or greater degree of symptoms. Change of greater than or equal to (>=) 10-points has been found to be clinically significant. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.
Adverse events
Toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.The number of Participants with adverse events will be recorded at each treatment visit.
Full Information
NCT ID
NCT03368131
First Posted
December 5, 2017
Last Updated
February 18, 2020
Sponsor
Hebei Medical University
1. Study Identification
Unique Protocol Identification Number
NCT03368131
Brief Title
Concurrent Neoadjuvant Chemoradiotherapy Plus Trastuzumab in the Treatment of Siewert II ，III of Human Epidermal Growth Factor Receptor-2(HER-2) Positive Gastroesophageal Junction Adenocarcinoma： A Randomized, Controlled Clinical Study
Official Title
A Prospective Study of Concurrent Neoadjuvant Chemoradiotherapy Plus Trastuzumab for Siewert II ，III of HER-2 Positive Adenocarcinoma at Gastroesophageal Junction
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Unknown status
Study Start Date
December 1, 2017 (Actual)
Primary Completion Date
December 30, 2019 (Actual)
Study Completion Date
December 31, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hebei Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of this study is to assess the efficacy and safety of patients who receive concurrent neoadjuvant chemoradiotherapy for Siewert II ，III of locally advanced HER-2 Positive adenocarcinoma at gastroesophageal junction
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastroesophageal Junction Adenocarcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Trastuzumab XELOX and radiotherapy
Arm Type
Experimental
Arm Description
Trastuzumab is intravenously administered with the loading dose of 8 mg/kg followed by maintenance dose of 6mg/kg in day 1 of each cycle. XELOX：Capecitabine 825~1000mg/m2 bid d1-14，Oxaliplatin 130 mg/m2 Ivgtt d1 q3w Radiotherapy：45 Gray (unit)Gy/25f （1.8Gy/f/d，5 f/w）
Arm Title
XELOX and radiotherapy
Arm Type
Active Comparator
Arm Description
Capecitabine：825~1000mg/m2 bid d1-14，Oxaliplatin 130 mg/m2 Ivgtt d1 q3w Radiotherapy：45Gy/25f （1.8Gy/f/d，5 f/w）
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Intervention Description
intravenously administered with the loading dose of 8 mg/kg followed by maintenance dose of 6mg/kg in day 1 of each cycle
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
825~1000mg/m2 bid d1-14
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
130 mg/m2 Ivgtt d1 q3w
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Intervention Description
45 Gray (unit) Gy/25f （1.8Gy/f/d，5 f/w）
Primary Outcome Measure Information:
Title
The pathological complete response rate(pCR)
Description
The lesion disappeared completely by pathology
Time Frame
within 3 weeks after surgery
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
Baseline to measured date of death from any cause
Time Frame
3 years
Title
Disease-free survival(DFS)
Description
Baseline to measured date of recurrence or death from any cause
Time Frame
3 years
Title
Disease Control Rate (DCR)
Description
Percentage of participants who achieved a best overall response of CR or PR or Stable Disease (SD).
Time Frame
3 years
Title
Percentage of Participants With Objective Response According to Modified Response Evaluation Criteria In Solid Tumors(mRECIST) v1.1
Description
Objective response referred to participants with complete response (CR) or partial response (PR). CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: greater than or equal to (>=) 30% decrease in sum of the longest diameter (LD) of all target lesions taking as reference the screening sum LD. To be assigned a status of PR or CR, changes in tumor measurements had to be confirmed by repeat assessments that should have been performed no less than 4 weeks after the criteria for response were first met. Longer intervals as determined by the study protocol were also appropriate. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.
Time Frame
within 3 weeks after surgery
Title
Percentage of Participants With Clinically Significant Improvement in European Organisation for Research and Treatment of Cancer Quality of Life Core Module 30 (EORTC Quality of Life Questionnaire (QLQ)-C30) Score
Description
The EORTC QLQ-C30 is a validated, cancer-specific 30-item patient-reported measure, and contains 14 domains to assess the impact of cancer treatment on 5 aspects of participants functioning (physical, role, cognitive, emotional, and social), 9 aspects of disease/treatment-related symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, loss of appetite, constipation, diarrhea) and a global QoL/overall health status scale. Questions used 4 point scale (1 'Not at all' to 4 'Very much'; with the exception of the QoL/health status scale which uses a 7-point scale (1 'very poor' to 7 'Excellent'). Each scale is transformed on a scale of 0-100; a higher score equals (=) a better level of functioning or greater degree of symptoms. Change of greater than or equal to (>=) 10-points has been found to be clinically significant. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.
Time Frame
Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at follow-up
Title
Adverse events
Description
Toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.The number of Participants with adverse events will be recorded at each treatment visit.
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age:18 to 60 years old (man or female);
confirmed to Siewert II , III of locally advanced adenocarcinoma at gastroesophageal junction. The her-2 positive was detected by immunohistochemistry or Fluorescence in SituHybridization(FISH);
Patients with Stage for Ⅲ by Endorectal Ultrasonography( EUS), Computed Tomography(CT) (or Positron Emission Tomography(PET )-CT) and laparoscopic (According to the eighth edition of American Joint Committee on Cancer (AJCC) );
Patients are diagnosed as potentially resectable by multidisciplinary team, no surgical contraindications, and expected to be surgical resection;
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
Major organ function has to meet the following criteria:
HB≥80g/L; ANC≥1.5×109/L; PLT≥90×109/L; Alanine Transaminase (ALT) and Aspartate Transaminase(AST)≤2.5×ULN, but<≤5×ULN if the transferase elevation is due to liver metastases； Total Bilirubin(TBIL)<1.5×ULN； Serum creatinine ≤1.5×ULN;Serum albumin ≥ 30g / L
Life expectancy greater than or equal to 6 months;
Participants were willing to join in this study, and written informed consent, good adherence, cooperate with the follow-up.
Exclusion Criteria:
Allergic to trastuzumab, capecitabine and oxaliplatin;
severe diseases such as liver and kidney，myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia，which affect the situation of chemotherapy or surgery
A variety of factors influencing oral drugs (such as unable to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction, etc);
Patients with tendency of gastrointestinal bleeding, including the following: a local active ulcerative lesions, and defecate occult blood (+ +); Has melena and hematemesis in two months;
Coagulant function abnormality (International Normalized Ratio(INR) > 1.5 ULN, Activated Partial Thromboplastin Time(APTT ) > 1.5 ULN), with bleeding tendency;
Pregnant or lactating women;
Patients with other malignant tumors within 5 years (except for curable skin basal cell carcinoma and cervical carcinoma in situ);
History of psychiatric drugs abuse and can't quit or patients with mental disorders;
Less than 4 weeks from the last clinical trial;
The researchers think inappropriate.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qun Zhao
Organizational Affiliation
Hebei Medical University Fourth Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jun Wang
Organizational Affiliation
Hebei Medical University Fourth Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fourth Affiliated Hospital of Hebei Medical University
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
050011
Country
China
12. IPD Sharing Statement
Learn more about this trial
Concurrent Neoadjuvant Chemoradiotherapy Plus Trastuzumab in the Treatment of Siewert II ，III of Human Epidermal Growth Factor Receptor-2(HER-2) Positive Gastroesophageal Junction Adenocarcinoma： A Randomized, Controlled Clinical Study
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