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Pembrolizumab, Trastuzumab, HER2 Positive Gastric Cancer

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ClinicalTrials.gov Identifier: NCT02901301
Recruitment Status : Recruiting
First Posted : September 15, 2016
Last Update Posted : January 12, 2018
Sponsor:
Information provided by (Responsible Party):

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.


Condition or disease Intervention/treatment Phase
Gastric Cancer Drug: Pembrolizumab Drug: Trastuzumab Drug: Capecitabine Drug: Cisplatin Phase 1 Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 49 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study of First Line Pembrolizumab in Combination With Trastuzumab, Capecitabine, and Cisplatin in HER2 Positive Gastric Cancer
Study Start Date : October 2016
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: 4 combination
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
Drug: Pembrolizumab
200mg, IV, q3weeks, Day 1
Drug: Trastuzumab
6mg/kg (8mg loading dose), IV, q3weeks, Day 1
Drug: Capecitabine
1000mg/m2, PO, BID, Day 1-14
Drug: Cisplatin
80mg/m2 (level 1), IV, q3weeks, Day 1


Outcome Measures

Primary Outcome Measures :
  1. The recommended dose of phase II [ Time Frame: 4 weeks ]
  2. The overall response rate using RECIST 1.1 [ Time Frame: 6 weeks ]

Secondary Outcome Measures :
  1. Duration of response [ Time Frame: 1 year ]
  2. Time to response [ Time Frame: 6 weeks ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. 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.
  2. 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.
  3. Has a known history of active Bacillus Tuberculosis
  4. Hypersensitivity to pembrolizumab or any of its excipients.
  5. 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.
  6. 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.
  7. Has a known additional malignancy that is progressing or requires active treatment within 3 years.
  8. Has known active central nervous system metastases and/or carcinomatous meningitis.
  9. Has active autoimmune disease that has required systemic treatment in the past 2 years
  10. Has known history of, or any evidence of active, non-infectious pneumonitis.
  11. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  12. Has known active Hepatitis B or Hepatitis C
  13. Has received a live vaccine within 30 days of planned start of study therapy.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02901301


Contacts
Contact: Hyo Song Kim, Ph.D 82-2-2228-8124 hyosong77@yuhs.ac

Locations
Korea, Republic of
Severance Hospital, Yonsei University Health System Recruiting
Seoul, Korea, Republic of, 03722
Contact: Hyo Song Kim         
Sponsors and Collaborators
Yonsei University
More Information

Responsible Party: Hyun Cheol Chung, Professor, Yonsei University
ClinicalTrials.gov Identifier: NCT02901301     History of Changes
Other Study ID Numbers: 4-2016-0190
First Posted: September 15, 2016    Key Record Dates
Last Update Posted: January 12, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Pembrolizumab
Cisplatin
Capecitabine
Trastuzumab
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action