Study of Ramucirumab, Trastuzumab and Paclitaxel in Patients With HER2-positive Recurrent/Metastatic Gastric Cancer (HER-RAM Study)

May 18, 2021 updated by: Yonsei University

An Open-label, Multicenter Phase Ib/II Study of Ramucirumab in Combination With Trastuzumab and Weekly Paclitaxel in Patients With HER2-positive Recurrent/Metastatic Gastric Cancer

Human epidermal growth factor receptor 2 (HER2) is overexpressed or amplified in 10-20% of gastric or gastroesophageal junction cancer. Trastuzumab combined with fluorouracil and platinum has been established as first-line treatment for patients with HER2-positive gastric cancer. The role of trastuzumab in second-line treatment for HER2-positive gastric cancer has not yet been addressed. Here, we evaluated the safety and efficacy of adding trastuzumab to ramucirumab and paclitaxel combination as a second-line treatment in HER2-positive gastric cancer progressed after trastuzumab-containing chemotherapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
    • Seodaemun-gu
      • Seoul, Seodaemun-gu, Korea, Republic of, 03722
        • Yonsei University Health System, Severance Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Histologically or cytologically proven metastatic or locally advanced HER2-positive gastric cancer
  2. Documented disease progression after receiving prior line of trastuzumab-containing chemotherapy for gastric cancer
  3. Able and willing to give written informed consent and has signed the informed consent form (ICF), prior to performance of any trial activities.
  4. Eligible male and female subjects aged ≥19 years.
  5. Has measurable disease as determined by RECIST 1.1.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  7. Has baseline left ventricular ejection fraction (LVEF) ≥ 55%.
  8. Adequate organ function as demonstrated by laboratory test results within 14 days prior to first dose of study treatment.
  9. Have urinary protein that is <2 on dipstick or routine urinalysis.
  10. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to first dose of study treatment.
  11. Female subjects of childbearing potential and male subjects should be willing to use methods of birth control for the course of the study and up to 120 days after the last dose of study treatment.

Exclusion Criteria:

  1. Received prior anticancer treatment with targeted agents, chemotherapy, or radiotherapy within 14 days, with monoclonal antibodies within 28 days, has previously received treatment with ramucirumab, or has participated in another clinical trial within 14 days prior to start of study treatment.
  2. Has experienced any Grade 3-4 gastrointestinal bleeding within 3 months prior to treatment.
  3. Has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 3 months prior to treatment.
  4. Has history of severe thromboembolism, including deep vein thrombosis and pulmonary embolism within 6 months prior to treatment.
  5. Has an active or ongoing infection, symptomatic congestive heart failure, uncontrolled angina pectoris, symptomatic or poorly controlled arrhythmia, uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled medical disorders in the opinion of the investigator.
  6. Has ongoing or active psychiatric illness or social situation that would limit compliance with study requirements.
  7. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  8. Has evidence of active, non-infectious pneumonitis.
  9. Has a known history of Human Immunodeficiency Virus (HIV).
  10. Has known active hepatitis B or hepatitis C.
  11. Have an elective or a planned major surgery during the course of the trial or has undergone major surgery within 4 weeks prior to enrollment.
  12. Has history of GI perforation and/or fistula within 6 months prior to treatment.
  13. Is pregnant or breastfeeding, or possibly pregnant.
  14. Has history of Child-Pugh Class B or more of liver cirrhosis or hepatic encephalopathy, or cirrhosis with clinically meaningful ascites.
  15. Is undergoing long-term antiplatelet therapy within 7 days prior to treatment.
  16. Has known history of hypersensitivity to one or more of the study treatments or their substances, or known severe hypersensitivity to monoclonal antibodies.
  17. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Study treatment
(Phase Ib part) Trastuzumab 4 mg/kg (loading dose) followed by 2 mg/kg IV, ramucirumab 8 mg/kg IV, and paclitaxel 80 or 70 mg/m2 IV (according to dose level) (Phase II part) Trastuzumab 4 mg/kg (loading dose) followed by 2 mg/kg IV, ramucirumab 8 mg/kg IV, and paclitaxel at RP2D (80 or 70 mg/m2 IV)
Drug: Trastuzumab + Ramucirumab + Paclitaxel
For both Phase Ib and II: Trastuzumab 4 mg/kg (loading dose) followed by 2 mg/kg on Days 1, 8, 15 and 22, and ramucirumab 8 mg/kg on Days 1 and 15, as well as paclitaxel will be administered intravenously in a 4-week cycle (every 28 days) For Phase Ib, Paclitaxel 80 or 70 mg/m2 (according to dose level) will be administered on Days 1, 8, 15 For Phase II, paclitaxel at RP2D (80 or 70 mg/m2) will be administered on Days 1, 8, 15 of each cycle

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Phase 1b: Maximum tolerated dose of trastuzumab, ramucirumab, and paclitaxel combination treatment in patients with HER2-positive gastric cancer
Time Frame: Phase 1b: During the first 4 weeks of treatment
Phase 1b: During the first 4 weeks of treatment
Phase 2: Progression-free survival in patients with HER2-positive gastric cancer receiving trastuzumab, ramucirumab, and paclitaxel combination treatment
Time Frame: Phase 2: At 24 weeks after start of treatment
Phase 2: At 24 weeks after start of treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Overall survival
Time Frame: through study completion, an average of 2 years
through study completion, an average of 2 years
Objective response rate according to RECIST 1.1
Time Frame: through study completion, an average of 2 years
through study completion, an average of 2 years
Disease control rate according to RECIST 1.1
Time Frame: through study completion, an average of 2 years
through study completion, an average of 2 years
Safety and tolerability based on incidence of treatment-emergent adverse events as assessed by CTCAE v4.02
Time Frame: Throughout the overall study period as well as up to 3 months after the last dose study treatment for each subject
Throughout the overall study period as well as up to 3 months after the last dose study treatment for each subject

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yonsei University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 13, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 2, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 2, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 9, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 14, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 17, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 21, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 18, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 4-2017-0275

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings