Trastuzumab Beyond Progression in HER2 Positive Metastatic Gastric Cancer

NCT03766607 | Withdrawn Phase 2

• 1 other identifier: KSWOG 1018
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival, PFS

  as measured from the start of the treatment to the date of either documentation of disease progression or death

  up to 12 months

Secondary Outcomes (3)

• Objective response rate, ORR

  up to 6 months

• Overall survival, OS

  up to 12 months

• Adverse event

  up to 12 months

Study Arms (1)

Trastuzumab with Ramucirumab and Paclitaxel

EXPERIMENTAL

Single 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

Drug: Trastuzumab; Drug: Ramucirumab; Drug: Paclitaxel

Interventions

Trastuzumab DRUG

Trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) administered intravenously every 21 days

Trastuzumab with Ramucirumab and Paclitaxel

Ramucirumab DRUG

Ramucirumab 8 mg/kg administered intravenously on days 1 and 15 every 28 days

Trastuzumab with Ramucirumab and Paclitaxel

Paclitaxel DRUG

Paclitaxel 80 mg/m2 administered intravenously on days 1, 8, and 15 every 28 days

Trastuzumab with Ramucirumab and Paclitaxel

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Over 19 years old
• Histologically confirmed HER2 overexpressing gastric cancer (HER2 overexpression is defined as IHC 3+ or FISH +)
• Metastatic gastric cancer
• 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.)
• At least one measurable or evaluable lesion according to RECIST ver 1.1
• ECOG performance status 0 or 1
• 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
• Life expectancy is more than 12 weeks
• Echocardiography at the time of enrollment showed an ejection fraction ≥ 50%
• 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)
• If the urine pregnancy test or serum beta-hCG result is negative in child bearing women
• If the subject have signed the informed consent form approved by the IRB

You may not qualify if:

• 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)
• Active virus, bacteria, or fungal infection (exception: HBV DNA titer is in the normal range for chronic hepatitis B carriers)
• If previous chemotherapy or radiotherapy was applied within 3 weeks before the administration of study drug
• If the subject has received major surgery within 4 weeks and the recovery is not complete before the administration of study drug
• 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)
• QTc interval \> 480 msec, long or short QT syndrome, or Burgada syndrome. In addition, known prolongation of QTc interval or Torsade de Pointes
• 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.
• History of symptomatic interstitial pneumonia
• 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.)

Sponsors & Collaborators

• Korean South West Oncology Group: lead

Study Sites (1)

Chonbuk National University Hospital

Jeonju, Jeollabuk-do, 54907, South Korea

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Trastuzumab; Ramucirumab; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Eun-Kee Song

  Korean Southwest Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: December 6, 2018
• Study Start: September 30, 2019
• Primary Completion: December 31, 2021
• Study Completion: June 30, 2022
• Last Updated: September 19, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)