Clinical Trials /

Trastuzumab Beyond Progression in HER2 Positive Metastatic Gastric Cancer

NCT03766607

Description:

The aim of this study is to evaluate the efficacy and safety of combination therapy with ramucirumab, paclitaxel, and trastuzumab biosimilar as second line treatment of HER2 positive metastatic gastric cancer after failure of first line chemotherapy including trastuzumab. This study is a phase II, single-arm, open label, multi-center study.

Related Conditions:
  • Gastric Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trastuzumab Beyond Progression in HER2 Positive Metastatic Gastric Cancer
  • Official Title: A Multi-center Phase II Study of Trastuzumab Biosimilar (SB3®) in Combination With Ramucirumab and Paclitaxel in HER2 Positive Metastatic Gastric Cancer Patients

Clinical Trial IDs

  • ORG STUDY ID: KSWOG 1018
  • NCT ID: NCT03766607

Conditions

  • Gastric Cancer

Interventions

DrugSynonymsArms
TrastuzumabTrastuzumab with Ramucirumab and Paclitaxel
RamucirumabTrastuzumab with Ramucirumab and Paclitaxel
PaclitaxelTrastuzumab with Ramucirumab and Paclitaxel

Purpose

The aim of this study is to evaluate the efficacy and safety of combination therapy with ramucirumab, paclitaxel, and trastuzumab biosimilar as second line treatment of HER2 positive metastatic gastric cancer after failure of first line chemotherapy including trastuzumab. This study is a phase II, single-arm, open label, multi-center study.

Detailed Description

      Approximately 15% of patients with advanced gastric cancer have HER2 overexpression and the
      combined use of trastuzumab and other cytotoxic chemotherapeutic agents, such as 5-FU and
      cisplatin, in these patients is associated with a significantly improved survival rate
      compared with cytotoxic chemotherapy alone. So, the combination of trastuzumab and
      chemotherapy is currently being used as a standard treatment in HER2 positive advanced
      gastric or gastroesophageal adenocarcinoma. However, after failing first line treatment with
      such regimen, second line treatment is determined regardless of HER2 status, and the most
      preferred treatment is ramucirumab and paclitaxel combination chemotherapy.

      Recently, the use of trastuzumab in combination with other cytotoxic chemotherapeutic agents
      has been reported to be superior to the use of cytotoxic chemotherapy alone in the treatment
      of patients with HER2 positive metastatic breast cancer. On the basis of several guidelines,
      it is recommended to extend the use of trastuzumab after disease progression. In addition, in
      some retrospective studies of metastatic gastric cancer, it has been reported that treatment
      with trastuzumab in combination with second line chemotherapy followed by first line
      chemotherapy including trastuzumab is beneficial and it is worthwhile to be tested in the
      prospective study. Furthermore, data on the safety and efficacy of cross-administration of
      trastuzumab biosimilar have not been available yet.
    

Trial Arms

NameTypeDescriptionInterventions
Trastuzumab with Ramucirumab and PaclitaxelExperimentalSingle arm study of trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) every 21 days + ramucirumab (8 mg/kg) on days 1 & 15 every 28 days + paclitaxel (80 mg/m2) on days 1, 8, and 15 every 28 days
  • Trastuzumab
  • Ramucirumab
  • Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          1. Over 19 years old

          2. Histologically confirmed HER2 overexpressing gastric cancer (HER2 overexpression is
             defined as IHC 3+ or FISH +)

          3. Metastatic gastric cancer

          4. Progressive disease has been confirmed after first line treatment including
             trastuzumab (If the recurrence occurred within 6 months after the completion of
             postoperative adjuvant therapy, it can be considered as first line treatment.)

          5. At least one measurable or evaluable lesion according to RECIST ver 1.1

          6. ECOG performance status 0 or 1

          7. Appropriate major organ function as defined below, A. Absolute neutrophil count (ANC)
             ≥ 1,500/mm3 B. Platelet ≥ 100,000/mm3 C. Hemoglobin > 8.0 g/dL D. Total bilirubin ≤
             1.5 x ULN E. AST and ALT < 3 x ULN (if there is a live metastasis, AST and ALT ≤ 5 x
             ULN) F. Serum creatinine ≤ 1.5x ULN or CCr > 50 mL/min

          8. Life expectancy is more than 12 weeks

          9. Echocardiography at the time of enrollment showed an ejection fraction ≥ 50%

         10. Previous adverse events of chemotherapy or radiotherapy has been resolved to less than
             grade 1 toxicity (exception: Alopecia, stable peripheral neuropathy, and manageable
             electrolyte imbalance by replacement therapy are acceptable if they are resolved to
             less than grade 2)

         11. If the urine pregnancy test or serum beta-hCG result is negative in child bearing
             women

         12. If the subject have signed the informed consent form approved by the IRB

        Exclusion Criteria:

          1. Symptomatic or unstable CNS metastasis (exception: appropriately treated brain
             metastasis without progression of more than 4 weeks after previous CT or MRI, and no
             steroid treatment for symptom relief is necessary)

          2. Active virus, bacteria, or fungal infection (exception: HBV DNA titer is in the normal
             range for chronic hepatitis B carriers)

          3. If previous chemotherapy or radiotherapy was applied within 3 weeks before the
             administration of study drug

          4. If the subject has received major surgery within 4 weeks and the recovery is not
             complete before the administration of study drug

          5. If there is a history of other malignancies within 3 years (exception: cervical
             intraepithelial cancer, well differentiated thyroid cancer, or skin cancer has been
             treated completely)

          6. QTc interval > 480 msec, long or short QT syndrome, or Burgada syndrome. In addition,
             known prolongation of QTc interval or Torsade de Pointes

          7. If there is a significant history of cardiovascular disease within 6 months, such as,
             myocardial infarction, unstable angina, significant cardiac arrhythmia, and
             uncontrolled hypertension (systolic BP > 180 mmHg, diastolic BP > 100 mmHg),
             congestive heart failure (NYHA class III-IV), pericardial effusion or pericardial
             tamponade, cardiomyopathy, cerebrovascular disease including transient ischemic
             stroke, and symptomatic pulmonary embolism.

          8. History of symptomatic interstitial pneumonia

          9. History of other psychiatric problems, abnormalities of laboratory test which have
             potential effects on administration of study drugs or participation on the study, or
             if the subject is inappropriate to be participated according to the investigator's
             decision (refusal to request and instruction, incooperative attitudes, etc.)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival, PFS
Time Frame:up to 12 months
Safety Issue:
Description:as measured from the start of the treatment to the date of either documentation of disease progression or death

Secondary Outcome Measures

Measure:Objective response rate, ORR
Time Frame:up to 6 months
Safety Issue:
Description:defined as the proportion of subjects who have a best overall response of complete response or partial response as assessed by RECIST 1.1
Measure:Overall survival, OS
Time Frame:up to 12 months
Safety Issue:
Description:defined as the time from the date of randomization until the date of death from any cause
Measure:Adverse event
Time Frame:up to 12 months
Safety Issue:
Description:as measured by NCI-CTCAE v5.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Korean South West Oncology Group

Last Updated