Open Actively Recruiting

Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-811/KEYNOTE-811)

About

Brief Summary

The purpose of this study is to: ; Compare the combination of trastuzumab with pembrolizumab and chemotherapy versus trastuzumab with placebo and chemotherapy ; Test the safety of the study drugs, to see how well the drug works and how the body handles the drug. Subjects will be put into a double-blind treatment group by chance, similar to flipping a coin, in order to decide what type of study drug they will receive: ; Group A: pembrolizumab and trastuzumab with chemotherapy ; Group B: Placebo and trastuzumab with chemotherapy Subjects will know which chemotherapy they are receiving. The chemotherapy will consist of one of the following regimens, which the study doctor will decide: ; FP Dose: cisplatin and 5-FU ; CAPOX Dose: capecitabine and oxaliplatin The following study drugs will be infused intravenously (through a vein) on Day 1 of every Cycle (21 days): ; Pembrolizumab/Placebo ; Trastuzumab ; Cisplatin, ; 5-Fluorouracil (5-FU) ; Oxaliplatin Capecitabine is an oral drug and should be taken during Days 1-14 of each cycle. We plan to enroll approximately 10 subjects at UCLA and 732 study wide

Primary Purpose
Treatment
Study Type
Interventional
Phase
Phase III

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
18 Years
Maximum Age
N/A

Adult patients diagnosed with HER2 positive advanced gastric or gastroesophageal junction cancer. For more information about the eligibility criteria for this trial, refer to the Health Professional version.

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2 positive gastric or GEJ adenocarcinoma
  • HER2-positive defined as either immunohistochemistry (IHC) 3+ or IHC 2+ in combination with in-situ hybridization positive (ISH+) or fluorescent in-situ hybridization (FISH), as assessed by central review on primary or metastatic tumor
  • Has measurable disease as defined by RECIST 1.1 as determined by the site investigator
  • Male participants must agree to use approved contraception
  • Female participants who are not pregnant or breastfeeding, and who are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception
  • Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to the first dose of trial treatment
  • Has a life expectancy of greater than 6 months
  • Has adequate organ function

Exclusion Criteria:

  • Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer
  • Has had major surgery, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment
  • Has had radiotherapy within 14 days of randomization
  • Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis)
  • Has an active infection requiring systemic therapy
  • Has poorly controlled diarrhea
  • Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment. If the participant is receiving diuretic drugs for other reasons, it is acceptable
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
  • Has peripheral neuropathy > Grade 1
  • Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
  • A WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation
  • Has active or clinically significant cardiac disease
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab, trastuzumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum-containing products
  • Has had an allogeneic tissue/solid organ transplant
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, Cluster of Differentiation 137 [CD137])

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Study Stats
Protocol No.
18-001594
Category
Hematology-Oncology
Oncology
Contact
Lisa Yonemoto
Location
  • UCLA Santa Monica
  • UCLA Westwood
For Providers
NCT No.
NCT03615326
For detailed technical eligibility, visit ClinicalTrials.gov.