Clinical Trials /

A Study of Epacadostat, an IDO1 Inhibitor, in Combination With Pembrolizumab in Patients With Metastatic and/or Locally Advanced Sarcoma

NCT03414229

Description:

The purpose of this study is to test any good and bad effects of the combination therapy of epacadostat and pembrolizumab and to determine how well the combination therapy works in the treatment of patients with sarcoma.

Related Conditions:
  • Sarcoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Epacadostat, an IDO1 Inhibitor, in Combination With Pembrolizumab in Patients With Metastatic and/or Locally Advanced Sarcoma
  • Official Title: Phase II Study of Epacadostat (INCB024360) in Combination With Pembrolizumab in Patients With Locally Advanced/Metastatic Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: 17-508
  • NCT ID: NCT03414229

Conditions

  • Sarcoma

Interventions

DrugSynonymsArms
EpacadostatUPS, Liposarcoma or pleomorphic liposarcoma
PembrolizumabUPS, Liposarcoma or pleomorphic liposarcoma

Purpose

The purpose of this study is to test any good and bad effects of the combination therapy of epacadostat and pembrolizumab and to determine how well the combination therapy works in the treatment of patients with sarcoma.

Trial Arms

NameTypeDescriptionInterventions
UPS, Liposarcoma or pleomorphic liposarcomaExperimentalUndifferentiated Pleomorphic Sarcoma (UPS) or Liposarcoma (dedifferentiated or pleomorphic liposarcoma) Epacadostat 100mg Twice daily Continuously days 1-21 of each 3 week cycle Oral Pembrolizumab 200mg Every 3 weeks Day 1 of each 3 week cycle IV infusion
  • Epacadostat
  • Pembrolizumab
LeiomyosarcomaExperimentalEpacadostat 100mg Twice daily Continuously days 1-21 of each 3 week cycle Oral Pembrolizumab 200mg Every 3 weeks Day 1 of each 3 week cycle IV infusion
  • Epacadostat
  • Pembrolizumab
Vascular Sarcoma SubtypesExperimentalIncluding angiosarcoma and Epithelioid Hemangioendothelioma (EHE). Epacadostat 100mg Twice daily Continuously days 1-21 of each 3 week cycle Oral Pembrolizumab 200mg Every 3 weeks Day 1 of each 3 week cycle IV infusion
  • Epacadostat
  • Pembrolizumab
OtherExperimentalEpacadostat 100mg Twice daily Continuously days 1-21 of each 3 week cycle Oral Pembrolizumab 200mg Every 3 weeks Day 1 of each 3 week cycle IV infusion
  • Epacadostat
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female age ≥ 18 years at the time of informed consent

          -  Be willing and able to provide written informed consent/assent for the trial

          -  Be willing to comply with treatment protocol

          -  Subjects must have a histologically confirmed metastatic and/or locally advanced
             sarcoma

          -  Adequate performance status: ECOG 0 or 1/KPS 100-70%

          -  Subjects must have at least one prior line of systemic therapy (e.g. chemotherapy,
             immunotherapy, targeted or biological therapy) for their sarcoma. An exception to this
             criterion will be made for patients with sarcoma histological subtypes for which there
             is no known standard systemic therapy (e.g., chondrosarcoma). Any patient that refuses
             standard chemotherapy for the treatment of their disease is also considered eligible.
             Prior adjuvant therapy will not count provided it was completed more than 6 months
             previously.

          -  Presence of measureable disease per RECIST v1.1.Target lesions must not be chosen from
             a previously irradiated field unless there has been radiographically and/or
             pathologically documented tumor progression in that lesion prior to enrollment.

          -  All subjects must agree to pre-treatment tumor biopsy. Subjects in whom biopsy is
             technically not feasible or in whom would result in unacceptable risk, in the opinion
             of the investigator, may be exempted from the biopsy requirement with discussion with
             the principal investigator.

          -  Adequate organ function determined within 21 days of treatment initiation

          -  Hematological

               -  Absolute neutrophil count (ANC) ≥1,000 /mcL

               -  Platelets ≥75,000 / mcL

               -  Hemoglobin ≥8 g/dL or ≥5.0 mmol/L

          -  Renal

             °Serum creatinine OR Measured or calculateda creatinine clearance (GFR can also be
             used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR

             ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN aCreatinine
             clearance should be calculated per institutional standard.

          -  Hepatic

               -  Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with
                  total bilirubin levels > 1.5 ULN

               -  AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver
                  metastases

               -  Albumin ≥ 2.5 mg/dL

          -  Coagulation

               -  International Normalized Ratio 52 or Prothrombin Time ≤1.5 X ULN unless subject
                  is receiving anticoagulant therapy as long as PT or PTT is within therapeutic
                  range of intended use of anticoagulants

               -  Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is
                  receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
                  of intended use of anticoagulants

          -  Women of childbearing potential must have a negative serum pregnancy test at screening
             and ≤ 72 hours prior to day 1 of study treatment.

          -  Male and female subjects of childbearing potential must be willing to use an adequate
             method of contraception as outlined in Section 11.7, for the course of the study
             through 120 days after the last dose of study medication.

        Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
        for the subject.

        Exclusion Criteria:

          -  Uncontrolled intercurrent illness including current active infection requiring
             systemic therapy or symptomatic congestive heart failure within 6 months

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment. This exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability.

          -  Evidence of clinically significant immunosuppression such as the following:

               -  Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease

               -  Concurrent opportunistic infection

               -  Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid
                  doses > 10 mg/day of prednisone or equivalent within 7 days prior to enrollment.
                  However, in the setting of non-immune mediated indications for steroid use,
                  chronic/active low dose steroid use may be permitted at the discretion of the
                  principal investigator. The dose of steroid allowed in this setting is also at
                  the discretion of the principal investigator. (Use of inhaled or topical steroids
                  is permitted.)

          -  History or evidence of symptomatic autoimmune disease (e.g., pneumonitis,
             glomerulonephritis, vasculitis, or other), or history of active autoimmune disease
             that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive
             drugs or biological agents used for treatment of autoimmune diseases) in past 2 years
             prior to enrollment. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin
             for diabetes or physiologic corticosteroid replacement therapy for adrenal or
             pituitary insufficiency) is not considered a form of systemic treatment for autoimmune
             disease.

          -  Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) disease

          -  Has known active Hepatitis B (e.g., Hepatitis B Virus PCR is detected) or Hepatitis C
             (e.g., HCV RNA [qualitative] is detected).

          -  Patients who have received a live vaccine within 30 days of the start date of the
             planned study therapy. Examples of live vaccines include, but are not limited to, the
             following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus
             Calmette-Guérin (BCG), and typhoid vaccine. 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.

          -  Has a known history of active TB (Bacillus Tuberculosis)

          -  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 2 weeks of the first dose of treatment.

          -  Has had a prior chemotherapy, immunotherapy, biological therapy, targeted small
             molecule therapy, or radiation therapy within 3 weeks prior to study Day 1 or who has
             not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to previously
             administered agent.

               -  Note: Subjects with ≤ Grade 2 neuropathy, alopecia or hypothyroidism are an
                  exception to this criterion and may qualify for the study.

               -  Note: If subject received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting therapy
                  events due to a previously administered agent.

          -  Presence of a gastrointestinal condition that may affect drug absorption

          -  Known allergy or reaction to any component of either study drug formulation

          -  Women who are pregnant or breast feeding

          -  Subjects 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 study treatment(s).

          -  Inability to comply with protocol required procedures

          -  Subjects receiving Monoamine Oxidase Inhibitors (MAOIs) or drug which has significant
             MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before
             screening.

          -  Any history of Serotonin Syndrome (SS) after receiving serotonergic drugs.

          -  History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's
             opinion, is clinically meaningful. Screening QTc interval 480 milliseconds is
             excluded. In the event that a single QTc is ≥ 480 milliseconds, the subject may enroll
             if the average QTc for the 3 ECGs is < 480 milliseconds. For subjects with an
             intraventricular conduction delay (QRS interval > 120 milliseconds), the JTc interval
             may be used in place of the QTc with the approval of the principal investigator. The
             JTc must be < 340 milliseconds if JTc is used in place of the QTc. Subjects with left
             bundle branch block are excluded.

        Note: QTc prolongation due to pacemaker may enroll if the JTc is normal.

          -  Use of any UGT1A9 inhibitor from screening through follow-up period, including the
             following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid.

          -  History of prior therapy with an IDO1 inhibitor in combination with an
             anti-PD-1/anti-PD-L1 agent/any other drug specifically targeting checkpoint pathways.
             Patients who have received prior therapy with single agent anti-PD-1/anti-PD-L1
             therapy or single agent IDO1 inhibitor will be eligible for this study.

          -  Presence of any other concurrent active malignancy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:number of patients with best objective response rate
Time Frame:by 24 weeks
Safety Issue:
Description:by RECIST 1.1.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Epacadostat
  • Pembrolizumab
  • 17-508

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