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Pembrolizumab, Trastuzumab, HER2 Positive Gastric Cancer

Primary Purpose

Gastric Cancer

Status

Unknown status

Phase

Phase 1

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Pembrolizumab

Trastuzumab

Capecitabine

Cisplatin

About this trial

This is an interventional treatment trial for Gastric Cancer

Eligibility Criteria

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

Inclusion Criteria:

HER2 positive advanced gastric cancer
Be willing and able to provide written informed consent/assent for the trial.
Be 19 years of age on day of signing informed consent.
Have measurable disease based on RECIST 1.1.
performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale.
Demonstrate adequate organ function
Female subject of childbearing potential should have a negative urine or serum pregnancy or be willing to use birth control.

Exclusion Criteria:

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
Has a known history of active Bacillus Tuberculosis
Hypersensitivity to pembrolizumab or any of its excipients.
Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier.
Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered from adverse events due to a previously administered agent.
Has a known additional malignancy that is progressing or requires active treatment within 3 years.
Has known active central nervous system metastases and/or carcinomatous meningitis.
Has active autoimmune disease that has required systemic treatment in the past 2 years
Has known history of, or any evidence of active, non-infectious pneumonitis.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Has known active Hepatitis B or Hepatitis C
Has received a live vaccine within 30 days of planned start of study therapy.

Sites / Locations

Severance Hospital, Yonsei University Health System

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

4 combination

Arm Description

pembrolizumab 200mg, IV, q3weeks, Day 1 trastuzumab 6mg/kg (8mg loading dose), IV, q3weeks, Day 1 capecitabine 1000mg/m2, PO, BID, Day 1-14 cisplatin 80mg/m2 (level 1), IV, q3weeks, Day 1

Outcomes

Primary Outcome Measures

The recommended dose of phase II

The overall response rate using RECIST 1.1

Secondary Outcome Measures

Duration of response

Time to response

Full Information

NCT ID

NCT02901301

First Posted

September 11, 2016

Last Updated

April 1, 2021

Sponsor

Yonsei University

1. Study Identification

Unique Protocol Identification Number

NCT02901301

Brief Title

Pembrolizumab, Trastuzumab, HER2 Positive Gastric Cancer

Official Title

A Phase Ib/II Study of First Line Pembrolizumab in Combination With Trastuzumab, Capecitabine, and Cisplatin in HER2 Positive Gastric Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Unknown status

Study Start Date

February 6, 2017 (Actual)

Primary Completion Date

October 31, 2020 (Actual)

Study Completion Date

October 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Yonsei University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Gastric cancer is one of the major health problems worldwide, and one of the leading cause of death especially in Asia. Though the cytotoxic chemotherapy is the main treatment option, newer and molecularly targeted agents are recently incorporated to improve the survival outcome. Human epidermal growth factor receptor 2 (HER2, ErbB2) is a transmembrane tyrosine kinase receptor and is overexpressed or amplified in 10-20% of gastric cancer. Recently, Trastuzumab for Gastric Cancer (ToGA) study reported the clinical benefit of trastuzumab for HER2 positive gastric cancer patients. However, because the majority of patients develop intrinsic or acquired resistance within 1 year, elucidating the molecular mechanisms for trastuzumab resistance is warranted to improve the survival outcome of HER2 positive gastric cancer patients. A growing body of preclinical and clinical evidence shows that the immune system contributes substantially to the therapeutic effects of "monoclonal antibody, trastuzumab" in solid tumors. Pembrolizumab is a potent and highly selective humanized monoclonal antibody designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Based on strong rationale in exploring the impact of combining trastuzumab with anti-PD-1 inhibitor in HER2 positive cancer, we suggest multicenter phase IB/II study to determine antitumor activity and safety of pembrolizumab in combination with standard treatment (trastuzumab, capecitabine, and cisplatin) in patients with HER2 positive gastric cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastric Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

41 (Actual)

8. Arms, Groups, and Interventions

Arm Title

4 combination

Arm Type

Experimental

Arm Description

pembrolizumab 200mg, IV, q3weeks, Day 1 trastuzumab 6mg/kg (8mg loading dose), IV, q3weeks, Day 1 capecitabine 1000mg/m2, PO, BID, Day 1-14 cisplatin 80mg/m2 (level 1), IV, q3weeks, Day 1

Intervention Type

Drug

Intervention Name(s)

Pembrolizumab

Intervention Description

200mg, IV, q3weeks, Day 1

Intervention Type

Drug

Intervention Name(s)

Trastuzumab

Intervention Description

6mg/kg (8mg loading dose), IV, q3weeks, Day 1

Intervention Type

Drug

Intervention Name(s)

Capecitabine

Intervention Description

1000mg/m2, PO, BID, Day 1-14

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

80mg/m2 (level 1), IV, q3weeks, Day 1

Primary Outcome Measure Information:

Title

The recommended dose of phase II

Time Frame

4 weeks

Title

The overall response rate using RECIST 1.1

Time Frame

6 weeks

Secondary Outcome Measure Information:

Title

Duration of response

Time Frame

1 year

Title

Time to response

Time Frame

6 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: HER2 positive advanced gastric cancer Be willing and able to provide written informed consent/assent for the trial. Be 19 years of age on day of signing informed consent. Have measurable disease based on RECIST 1.1. performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale. Demonstrate adequate organ function Female subject of childbearing potential should have a negative urine or serum pregnancy or be willing to use birth control. Exclusion Criteria: Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Has a known history of active Bacillus Tuberculosis Hypersensitivity to pembrolizumab or any of its excipients. Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered from adverse events due to a previously administered agent. Has a known additional malignancy that is progressing or requires active treatment within 3 years. Has known active central nervous system metastases and/or carcinomatous meningitis. Has active autoimmune disease that has required systemic treatment in the past 2 years Has known history of, or any evidence of active, non-infectious pneumonitis. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. Has known active Hepatitis B or Hepatitis C Has received a live vaccine within 30 days of planned start of study therapy.

Facility Information:

Facility Name

Severance Hospital, Yonsei University Health System

City

Seoul

ZIP/Postal Code

03722

Country

Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Pembrolizumab, Trastuzumab, HER2 Positive Gastric Cancer

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