Clinical Trials /

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

NCT03832569

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 18-399
  • NCT ID: NCT03832569

Conditions

  • Solid Tumors
  • Identified by NGS, PCR or IHC

Interventions

DrugSynonymsArms
PembrolizumabPembrolizumab
PlaceboPlacebo

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
PembrolizumabExperimentalPembrolizumab 200 mg IV every 3 weeks over 30 minutes.
  • Pembrolizumab
PlaceboPlacebo ComparatorPlacebo 200mg IV every 3 weeks over 30 minutes
  • Placebo

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:proportion of patients with ctDNA clearance
Time Frame:12 months post randomization
Safety Issue:
Description: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

Measure:disease free survival (DFS)
Time Frame:5 years
Safety Issue:
Description:DFS is defined as the time from treatment start till recurrence or death whichever comes first.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Pembrolizumab
  • 18-399

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