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Study of Pembrolizumab or Placebo Following Surgery in Patients With Microsatellite Instability High (MSI-H) Solid Tumors

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ClinicalTrials.gov Identifier: NCT03832569
Recruitment Status : Not yet recruiting
First Posted : February 6, 2019
Last Update Posted : February 6, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
The purpose of this study is to test the safety of the study drug, pembrolizumab, and to find out how well it works to prevent cancer from coming back in people who have had a solid tumor surgically removed, but still have tumor cells in their blood. During the study, the participant will receive either the study drug or a placebo for as long as 12 months, or until the cancer comes back, or the side effects of the treatment become too severe.

Condition or disease Intervention/treatment Phase
Solid Tumors Identified by NGS, PCR or IHC Drug: Pembrolizumab Drug: Placebo Phase 2

Study Type : Interventional
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a randomized, double-blind study of adjuvant pembrolizumab or placebo in patients with MSI-H solid tumors with persistent circulating tumor DNA (ctDNA) despite curative surgery and completion of standard perioperative and/or adjuvant therapy
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blind Study of Adjuvant Pembrolizumab or Placebo in Patients With MSI-H Tumors With Persistent Circulating Tumor DNA Following Surgery
Estimated Study Start Date : February 2019
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pembrolizumab
Pembrolizumab 200 mg IV every 3 weeks over 30 minutes.
Drug: Pembrolizumab
Pembrolizumab 200 mg IV every 3 weeks over 30 minutes.

Placebo Comparator: Placebo
Placebo 200mg IV every 3 weeks over 30 minutes
Drug: Placebo
Placebo 200mg IV every 3 weeks over 30 minutes




Primary Outcome Measures :
  1. proportion of patients with ctDNA clearance [ Time Frame: 12 months post randomization ]
    Patients who have ctDNA clearance at 12 months will be considered responders, and patients who do not have ctDNA clearance at 12 months will be considered non-responders.


Secondary Outcome Measures :
  1. disease free survival (DFS) [ Time Frame: 5 years ]
    DFS is defined as the time from treatment start till recurrence or death whichever comes first.



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

Inclusion Criteria:

  • Age 18 years or older
  • ECOG performance status 0-1
  • Sign informed consent within 3 months after curative surgery and completion of standard of care perioperative and/or adjuvant therapy.
  • Any solid tumor with MSI or MRD by IHC, PCR or NGS testing. MSKCC confirmation of MSI-H/MRD status is not mandatory prior to enrollment and treatment on the study. For patients with outside testing, if sufficient tissue is available NGS will be repeated at MSKCC and will not impact the patient's eligibility.
  • 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
  • To be eligible for pembrolizumab or placebo therapy, the patients must have positive ctDNA (as defined in section 7.0) within 4 months after completion of appropriate standard of care therapy (surgery, chemotherapy, radiation as appropriate). Note, if ctDNA has a negative result, ctDNA can be re-tested 4 weeks later, within 5 months of completion of standard therapy.
  • Demonstrate adequate organ function:

    • Absolute neutrophil count (ANC) ≥1,500 /mcL
    • Platelets ≥100,000 / mcL
    • Hemoglobin ≥9 g/dL
    • Serum creatinine ≤1.5 X upper limit of normal (ULN)
    • 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 (≤3x 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).
  • 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.

    o 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.

    o 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, unwillingness to participate, or inability 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 ClinicalTrials.gov identifier (NCT number): NCT03832569


Contacts
Contact: Yelena Janjigian, MD 646-888-4186 janjigiy@mskcc.org
Contact: Dmitriy Zamarin, MD, PhD 646-888-4882

Locations
United States, New Jersey
Memoral Sloan Kettering Basking Ridge Not yet recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Yelena Janjigian, MD         
Principal Investigator: Yelena Janjigian, MD         
Memoral Sloan Kettering Monmouth
Middletown, New Jersey, United States, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, United States, 07645
United States, New York
Memorial Sloan Kettering Commack
Commack, New York, United States, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, United States, 10604
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan Kettering Rockville Centre Not yet recruiting
Rockville Centre, New York, United States, 11570
Contact: Yelena Janjigian, MD    646-888-4186      
Principal Investigator: Yelena Janjigian, MD         
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Yelena Janjigian, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03832569     History of Changes
Other Study ID Numbers: 18-399
First Posted: February 6, 2019    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: February 2019
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 clinicaltrials.gov 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 following one year after publication and for up to 36 months later. 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: crdatashare@mskcc.org.
Supporting Materials: Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)

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:
Pembrolizumab
18-399

Additional relevant MeSH terms:
Microsatellite Instability
Genomic Instability
Pathologic Processes
Pembrolizumab
Antineoplastic Agents