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A Single-Arm Pilot Study of Adjuvant Pembrolizumab Plus Trastuzumab in HER2+ Esophagogastric Tumors With Persistent Circulating Tumor DNA Following Curative Resection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04510285
Recruitment Status : Recruiting
First Posted : August 12, 2020
Last Update Posted : July 14, 2021
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
The purpose of this study is to find out whether treatment with trastuzumab combined with pembrolizumab will improve the clearance of tumor DNA from participants' bodies after surgery.

Condition or disease Intervention/treatment Phase
Esophagogastric Tumors Gastric Cancer Gastric Tumor Esophageal Cancer Esophageal Neoplasms Esophageal Tumor GastroEsophageal Cancer Gastroesophageal Junction Adenocarcinoma Gastroesophageal Junction Tumor Gastroesophageal Junction Cancer Drug: Trastuzumab Drug: Pembrolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a single arm pilot study of adjuvant pembrolizumab + trastuzumab.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-Arm Pilot Study of Adjuvant Pembrolizumab Plus Trastuzumab in HER2+ Esophagogastric Tumors With Persistent Circulating Tumor DNA Following Curative Resection
Actual Study Start Date : August 10, 2020
Estimated Primary Completion Date : August 10, 2022
Estimated Study Completion Date : August 10, 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Trastuzumab and Pembrolizumab

Trastuzumab will be administered on an every 3 week dosing schedule, with initial loading dose of 8 mg/kg as a 90 minute infusion, followed by trastuzumab 6 mg/kg every 3 weeks.

The planned dose of pembrolizumab for this study is 200 mg every 3 weeks.

Drug: Trastuzumab
Trastuzumab (8mg/kg loading dose; 6mg/kg maintenance) will be administered on day 1 of each 3-week dosing cycle (21 days).

Drug: Pembrolizumab
Pembrolizumab 200 mg IV will be administered on day 1 of each 3-week dosing cycle (21 days).

Primary Outcome Measures :
  1. Rate of ctDNA clearance at 6 months [ Time Frame: 6 months ]

    The primary endpoint of the study is the proportion of patients with ctDNA clearance at 6 months with trastuzumab/pembrolizumab or trastuzumab/placebo in patients with HER2+ esophagogastric cancer with persistent ctDNA despite curative surgery and standard perioperative/adjuvant therapy.

    CtDNA clearance is the conversion of detectable to undetectable ctDNA

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age 18 years or older.
  • ECOG performance status 0-2.
  • Sign informed consent within 8 months after curative surgery and completion of standard of care perioperative and/or adjuvant therapy.
  • HER2+ esophageal, GEJ, or gastric adenocarcinoma biopsy or resection specimen as defined by local HER2 IHC3+ or IHC 2+/FISH>2.0 expression.
  • Must have genetic testing of DNA from primary tumor for somatic genomic alterations across a minimum of 50 genes.
  • Must have undergone a complete curative surgical resection (R0).
  • Must have completed standard of care (SOC) surgery, neoadjuvant or adjuvant therapy
  • CtDNA will be tested at a minimum of four weeks after completion of surgery and standard perioperative and/or adjuvant therapy. To be eligible for trastuzumab/pembrolizumab or trastuzumab therapy, the patients must have positive ctDNA (as defined in section 7.0) within 8 months after completion of appropriate standard of care therapy (surgery, chemotherapy, radiation as appropriate). For all patients, if the initial ctDNA has a negative result, ctDNA can be re-tested 4 weeks later, within 9 months of completion of standard therapy.
  • Demonstrate adequate organ function as defined in Table 1.

Hematological Absolute neutrophil Count (ANC): ≥ 1,500 /mcL Platelets: ≥ 100,000 /mcL Hemoglobin: ≥ 9 g/dL

Renal Serum creatinine ≤ 1.5 X upper limit of normal (ULN)

Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN. Except patients with Gilbert's disease (≤ 3 x ULN) AST and ALT ≤ 2.5 X ULN Albumin ≥ 3 mg/dL

Exclusion Criteria:

  • Patients who have not recovered from serious adverse events (as determined by treating MD) related to surgery.
  • Presence of metastatic or recurrent disease.
  • Had R1 (microscopic residual tumor) or R2 resection (macroscopic residual tumor at resection margin).
  • Left ventricular ejection fraction <50% within 1 month of screening by MUGA or echocardiogram.
  • 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.
  • Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone containing antiemetic regimen or steroids as CT scan contrast premedication) may be enrolled.
  • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
  • Has a known history of active TB (Bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

    ° Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has known history of, or any evidence of active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 agent.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease; systemic lupus erythematosus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves' disease; rheumatoid arthritis, hypophysitis, uveitis) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:

    • Subjects with vitiligo or alopecia
    • Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy.

    ° Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

  • Is unwilling to give written informed consent, unwilling to participate, or unable to comply with the protocol for the duration of the study.

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 identifier (NCT number): NCT04510285

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Contact: Yelena Y Janjigian, MD 646-888-4186
Contact: Daniela Molena, MD 212-639-3870

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United States, New Jersey
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Yelena Janjigian, MD    646-888-4186      
Principal Investigator: Yelena Janjigian, MD         
Memorial Sloan Kettering Monmouth (Limited Protocol Activities) Recruiting
Middletown, New Jersey, United States, 07748
Contact: Yelena Janjigian, MD    646-888-4186      
Memorial Sloan Kettering Bergen (Limited Protocol Activities) Recruiting
Montvale, New Jersey, United States, 07645
Contact: Yelena Janjigian, MD    646-888-4186      
United States, New York
Memorial Sloan Kettering Commack (Limited Protocol Activities) Recruiting
Commack, New York, United States, 11725
Contact: Yelena Janjigian, MD    646-888-4186      
Principal Investigator: Yelena Janjigian, MD         
Memorial Sloan Kettering Westchester (Limited Protocol Activities) Recruiting
Harrison, New York, United States, 10604
Contact: Yelena Janjigian, MD    646-888-4186      
Memorial Sloan Kettering Cancer Center (All Protocol Activities) Recruiting
New York, New York, United States, 10065
Contact: Yelena Y Janjigian, MD    646-888-4186      
Memorial Sloan Kettering Nassau (Limited Protocol Activities) Recruiting
Uniondale, New York, United States, 11553
Contact: Yelena Janjigian, MD    646-888-4186      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
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Principal Investigator: Yelena Y Janjigian, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center Identifier: NCT04510285    
Other Study ID Numbers: 20-158
First Posted: August 12, 2020    Key Record Dates
Last Update Posted: July 14, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to:

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Esophagogastric Tumors
Esophagogastric Cancers
Gastric Cancer
Esophageal Cancer
Gastroesophageal Junction Cancer
GEJ Tumor
Memorial Sloan Kettering Cancer Center
Additional relevant MeSH terms:
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Stomach Neoplasms
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents