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A Study of Trastuzumab in Combination With Capecitabine and Cisplatin in Patients With Tissue HER2- But Serum HER2+ AGC

Primary Purpose

Gastric or Gastroesophageal Junction(GEJ) Adenocarcinoma

Status
Recruiting
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Trastuzumab, Capecitabine and Cisplatin
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric or Gastroesophageal Junction(GEJ) Adenocarcinoma

Eligibility Criteria

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

Inclusion Criteria:

  1. Patients with inoperable, locally-advanced or recurrent and/or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma who are not eligible for curative therapy and are histologically diagnosed.
  2. Diseases measurable according to Response Evaluation Criteria in Solid Tumors (RECIST1.1) using imaging technique (CT or MRI).
  3. Tissue HER2-negative tumors (primary or metastatic tumors) defined as IHC2+ and FISH- or IHC 0 or 1+ according to gastric cancer assessment system for HER2 (see Annex 12.5).
  4. ECOG Performance status 0, 1 or 2 (see Annex 12.1).
  5. Survival for at least 3 months should be possible.
  6. Appropriate bone marrow, renal, and hepatic functions. General inclusion criteria
  7. Males or females aged 19 years.
  8. Patients should sign the informed consent form (ICF).

Exclusion Criteria:

  1. Patients who previously received chemotherapy for advanced/metastatic diseases (adjuvant/neoadjuvant chemotherapy, completed at least 6 months prior to enrollment in this clinical study, is permitted, but platinum-based adjuvant/neoadjuvant chemotherapy is not permitted).
  2. Patients with a lack of physical integration of the upper gastrointestinal tract or with a malabsorption syndrome (e.g., patients who underwent partial or total gastric resection can participate in this clinical study, but patients equipped with a jejunostomy tube cannot participate).
  3. Patients with active (serious or uncontrolled) gastrointestinal bleeding.
  4. Patients with relevant toxicities remaining following previous curative therapy (except for alopecia). For example, neurotoxicity ≥ grade 2 based on NCI-CTCAE version 5.0.
  5. Patients with a history of other malignant diseases based on the date of complete recovery within 5 years prior to the initiation of treatment in this clinical study (except for in-situ cervical cancer and basal cell carcinoma).

    Hematologic, blood chemistry, and organ functions

  6. Neutrophil count < 1.5 × 109/L, or platelet count < 100 × 109/L.
  7. Serum bilirubin> 1.5 × upper limit of normal (ULN); or AST or ALT > 2.5 × ULN (or > 5 × ULN hepatic metastasis patients); or alkaline phosphatase > 2.5 × ULN (or > 5 × ULN hepatic metastasis patients, or > 10 × ULN hepatic metastasis-free bone metastasis patients); or, albumin < 2.5 g/dL.
  8. Creatinine clearance < 60 mL/min. However, creatinine clearance is first calculated using the Cockroft-Gault formula, and if the value is < 60ml/min, a 24hr urine collection test is carried out. Subject enrollment is possible only when creatinine clearance is ≥ 60mL/min.

    Other investigational product-associated exclusion criteria

  9. History of proven congestive heart failure; angina pectoris in need of medication; evidence of transmural myocardial infarction through electrocardiogram (ECG); uncontrolled hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg); clinically significant heart valve disorders; and high-risk uncontrolled arrhythmia.
  10. Baseline left ventricular ejection fraction (LVEF) < 50% (measured with echocardiogram or MUGA).
  11. Patients with dyspnoea at rest due to advanced tumors or other diseases, or who need an adjuvant oxygen therapy.
  12. Patients who are treated with long-term or high-dose corticosteroids (steroid inhalation or short-term use of oral steroids for vomiting inhibition and appetite stimulation is permitted).
  13. Patients with Clinically significant hypoacusis
  14. Patients known to show dihydropyrimidine dehydrogenase (DPD) deficiency. General exclusion criteria
  15. Patients with a history of brain metastasis or clinical evidence.
  16. Uncontrolled serious systemic intercurrent diseases (e.g., infection or uncontrolled diabetes).
  17. Females who are pregnant or are breast-feeding.
  18. Fertile males and females who are unwilling to use effective contraceptive methods.
  19. Patients who are treated with another investigational product within 4 weeks prior to the initiation of treatment in this clinical study.
  20. Patients receiving radiation therapy within 4 weeks prior to the initiation of treatment with the study drug (palliative radiation curative therapy that is partially carried out for bone metastasis. Washout period of 2 weeks is also permitted in patients recovered from all acute toxicities.).
  21. Patients who underwent major surgery within 4 weeks prior to the initiation of treatment with the study drug and have not yet been completely recovered.
  22. Patients known to have HIV infectivity or active infection with HBV or HCV.
  23. Patients with hypersensitivity to the study drug.

Sites / Locations

  • Asan Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

treatment arm

Arm Description

Single arm

Outcomes

Primary Outcome Measures

Efficacy (Overall tumor response)
Overall tumor response (responder/non-responder) which is a primary efficacy endpoint: is defined as the maximal response among confirmed cases of complete response (CR) or partial response (PR) determined by definite radiological assessment of target and nontarget lesions in accordance with RECIST criteria version 1.1.

Secondary Outcome Measures

progression free survival
Time from the start date of chemotherapy to the date of disease progression or death of any cause which comes first
Duration of response
Time from the date of tumor response by RECIST version 1.1 to the date of disease progression
Overall Survival
Time from the start date of chemotherapy to the date of death of any cause
Time to disease progression
Time from the start date of chemotherapy to the date of disease progression
Safety(Toxicity profile)
Assessed by NCI CTCAE version 5.0

Full Information

First Posted
January 6, 2020
Last Updated
December 30, 2022
Sponsor
Asan Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT04309578
Brief Title
A Study of Trastuzumab in Combination With Capecitabine and Cisplatin in Patients With Tissue HER2- But Serum HER2+ AGC
Official Title
A Phase II Clinical Study of Trastuzumab in Combination With Capecitabine and Cisplatin (XP) in Patients With Tissue HER2-negative But Serum HER2-positive Advanced Gastric Cancer: XP+Samfenet
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 12, 2020 (Actual)
Primary Completion Date
March 31, 2023 (Anticipated)
Study Completion Date
March 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A phase II clinical study of trastuzumab in combination with capecitabine and cisplatin (XP) in patients with tissue HER2-negative but serum HER2-positive advanced gastric cancer
Detailed Description
3-weekly/ 1cycle treatment Trastuzumab intravenous administration at a loading dose of 8 mg/kg on day 1 followed by 6 mg/kg every 3 weeks Capecitabine oral administration at a dose of 1000 mg/m2 twice daily for 14 days every 3 weeks (from evening on day 1 to morning on day 15) Cisplatin intravenous administration at a dose of 80 mg/m2 on day 1

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric or Gastroesophageal Junction(GEJ) Adenocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
treatment arm
Arm Type
Experimental
Arm Description
Single arm
Intervention Type
Drug
Intervention Name(s)
Trastuzumab, Capecitabine and Cisplatin
Intervention Description
Trastuzumab intravenous administration at a loading dose of 8 mg/kg on day 1 followed by 6 mg/kg every 3 weeks Capecitabine oral administration at a dose of 1000 mg/m2 twice daily for 14 days every 3 weeks (from evening on day 1 to morning on day 15) Cisplatin intravenous administration at a dose of 80 mg/m2 on day 1
Primary Outcome Measure Information:
Title
Efficacy (Overall tumor response)
Description
Overall tumor response (responder/non-responder) which is a primary efficacy endpoint: is defined as the maximal response among confirmed cases of complete response (CR) or partial response (PR) determined by definite radiological assessment of target and nontarget lesions in accordance with RECIST criteria version 1.1.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
progression free survival
Description
Time from the start date of chemotherapy to the date of disease progression or death of any cause which comes first
Time Frame
2 years
Title
Duration of response
Description
Time from the date of tumor response by RECIST version 1.1 to the date of disease progression
Time Frame
2 years
Title
Overall Survival
Description
Time from the start date of chemotherapy to the date of death of any cause
Time Frame
2 years
Title
Time to disease progression
Description
Time from the start date of chemotherapy to the date of disease progression
Time Frame
2 years
Title
Safety(Toxicity profile)
Description
Assessed by NCI CTCAE version 5.0
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with inoperable, locally-advanced or recurrent and/or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma who are not eligible for curative therapy and are histologically diagnosed. Diseases measurable according to Response Evaluation Criteria in Solid Tumors (RECIST1.1) using imaging technique (CT or MRI). Tissue HER2-negative tumors (primary or metastatic tumors) defined as IHC2+ and FISH- or IHC 0 or 1+ according to gastric cancer assessment system for HER2 (see Annex 12.5). ECOG Performance status 0, 1 or 2 (see Annex 12.1). Survival for at least 3 months should be possible. Appropriate bone marrow, renal, and hepatic functions. General inclusion criteria Males or females aged 19 years. Patients should sign the informed consent form (ICF). Exclusion Criteria: Patients who previously received chemotherapy for advanced/metastatic diseases (adjuvant/neoadjuvant chemotherapy, completed at least 6 months prior to enrollment in this clinical study, is permitted, but platinum-based adjuvant/neoadjuvant chemotherapy is not permitted). Patients with a lack of physical integration of the upper gastrointestinal tract or with a malabsorption syndrome (e.g., patients who underwent partial or total gastric resection can participate in this clinical study, but patients equipped with a jejunostomy tube cannot participate). Patients with active (serious or uncontrolled) gastrointestinal bleeding. Patients with relevant toxicities remaining following previous curative therapy (except for alopecia). For example, neurotoxicity ≥ grade 2 based on NCI-CTCAE version 5.0. Patients with a history of other malignant diseases based on the date of complete recovery within 5 years prior to the initiation of treatment in this clinical study (except for in-situ cervical cancer and basal cell carcinoma). Hematologic, blood chemistry, and organ functions Neutrophil count < 1.5 × 109/L, or platelet count < 100 × 109/L. Serum bilirubin> 1.5 × upper limit of normal (ULN); or AST or ALT > 2.5 × ULN (or > 5 × ULN hepatic metastasis patients); or alkaline phosphatase > 2.5 × ULN (or > 5 × ULN hepatic metastasis patients, or > 10 × ULN hepatic metastasis-free bone metastasis patients); or, albumin < 2.5 g/dL. Creatinine clearance < 60 mL/min. However, creatinine clearance is first calculated using the Cockroft-Gault formula, and if the value is < 60ml/min, a 24hr urine collection test is carried out. Subject enrollment is possible only when creatinine clearance is ≥ 60mL/min. Other investigational product-associated exclusion criteria History of proven congestive heart failure; angina pectoris in need of medication; evidence of transmural myocardial infarction through electrocardiogram (ECG); uncontrolled hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg); clinically significant heart valve disorders; and high-risk uncontrolled arrhythmia. Baseline left ventricular ejection fraction (LVEF) < 50% (measured with echocardiogram or MUGA). Patients with dyspnoea at rest due to advanced tumors or other diseases, or who need an adjuvant oxygen therapy. Patients who are treated with long-term or high-dose corticosteroids (steroid inhalation or short-term use of oral steroids for vomiting inhibition and appetite stimulation is permitted). Patients with Clinically significant hypoacusis Patients known to show dihydropyrimidine dehydrogenase (DPD) deficiency. General exclusion criteria Patients with a history of brain metastasis or clinical evidence. Uncontrolled serious systemic intercurrent diseases (e.g., infection or uncontrolled diabetes). Females who are pregnant or are breast-feeding. Fertile males and females who are unwilling to use effective contraceptive methods. Patients who are treated with another investigational product within 4 weeks prior to the initiation of treatment in this clinical study. Patients receiving radiation therapy within 4 weeks prior to the initiation of treatment with the study drug (palliative radiation curative therapy that is partially carried out for bone metastasis. Washout period of 2 weeks is also permitted in patients recovered from all acute toxicities.). Patients who underwent major surgery within 4 weeks prior to the initiation of treatment with the study drug and have not yet been completely recovered. Patients known to have HIV infectivity or active infection with HBV or HCV. Patients with hypersensitivity to the study drug.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
YoonKoo Kang, MD, Ph.D
Phone
+82-2-3010-2043
Email
ykkang@amc.seoul.kr
First Name & Middle Initial & Last Name or Official Title & Degree
Min-Hee Ryu, MD, Ph.D
Phone
+82-2-3010-5935
Email
miniryu@amc.seoul.kr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yoon-Koo Kang, MD, PhD
Organizational Affiliation
Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asan Medical Center
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yoon-Koo Kang, MD, PhD
Phone
+82-2-3010-3230
Email
ykkang@amc.seoul.kr
First Name & Middle Initial & Last Name & Degree
Min-Hee Ryu, MD, PhD
Phone
+82-2-3010-5935
Email
miniryu@amc.seoul.kr

12. IPD Sharing Statement

Learn more about this trial

A Study of Trastuzumab in Combination With Capecitabine and Cisplatin in Patients With Tissue HER2- But Serum HER2+ AGC

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