Clinical Trials /

Epacadostat and Pembrolizumab in Treating Participants With Advanced Pancreatic Cancer

NCT03432676

Description:

This phase II trial studies how well epacadostat and pembrolizumab work in treating participants with pancreatic cancer that has spread to other places in the body. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving epacadostat and pembrolizumab may work better in treating participants with pancreatic cancer.

Related Conditions:
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of IDO-1 Inhibitor Epacadostat in Combination With Pembrolizumab in Advanced Pancreatic Cancer With Chromosomal Instability/ Homologous Recombination Repair Deficiency (HRD)
  • Official Title: Single-Arm, Phase II Proof of Concept Study of IDO-1 Inhibitor Epacadostat in Combination With Pembrolizumab in Advanced Pancreatic Cancer With Chromosomal Instability/ Homologous Recombination Repair Deficiency (HRD)

Clinical Trial IDs

  • ORG STUDY ID: 2016-0893
  • NCT ID: NCT03432676

Conditions

  • Pancreatic Adenocarcinoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, MK-3475, SCH-900475Pembrolizumab + Epacadostat
EpacadostatINCBO24360Pembrolizumab + Epacadostat

Purpose

The goal of this clinical research study is to learn if epacadostat in combination with pembrolizumab can help to control previously treated pancreatic ductal adenocarcinoma in patients who have a specific type of genetic change. This type of genetic change may mean you are more likely to respond to the study drugs. The safety of this combination will also be studied. This is an investigational study. Epacadostat is not FDA approved or commercially available. It is currently being used for research purposes only. Pembrolizumab is FDA approved and commercially available for the treatment of many types of cancer. It is investigational to use pembrolizumab to treat pancreatic ductal adenocarcinoma. The combination of these drugs is considered investigational. The study doctor can explain how the study drugs are designed to work. Up to 21 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Description

      Study Drug Administration:

      Each cycle is 21 days.

      You will receive pembrolizumab by vein over about 30 minutes on Day 1 of each cycle. After
      the first dose, you will stay in the clinic for an additional 60 minutes after the dose.
      After that, if no intolerable side effects occur, you will only stay in the clinic for an
      additional 30 minutes after each dose.

      You will take 2 epacadostat pills by mouth every day while on study. Tablets should be taken
      about 12 hours apart (1 morning dose, 1 evening dose) at the same time each day. Tablets
      should be swallowed whole; do not chew, crush, dissolve, or divide the tablets. If you vomit
      a dose of epacadostat, you may take a "make up" dose only if the tablets can be seen and
      counted. If you miss a dose of epacadostat, you may take the tablets as soon as you remember
      but only if it has not been more than 2 hours since your scheduled dose. If it has been more
      than 2 hours, wait and take your next dose as scheduled.

      You will be given a medication diary to keep track of when you take each dose of epacadostat.
      The study staff will tell you when you should bring the diary and any unused tablets to the
      clinic.

      Length of Study:

      You may continue taking the study drugs for as long as the doctor thinks it is in your best
      interest. You will no longer be able to take the study drugs if the disease gets worse, if
      intolerable side effects occur, or if you are unable to follow study directions.

      Your participation in this study will be over after follow-up (described below).

      Study Visits:

      On Day 1 of all cycles:

        -  You will have a physical exam.

        -  Blood (about 3 teaspoons) will be drawn for routine tests.

        -  During Cycles 1-5, blood (about 3 tablespoons) will be drawn for biomarker testing.

      On Days 8 and 15 of Cycle 1, blood (about 3 tablespoons) will be drawn for biomarker testing.

      Every 9 weeks for the first 36 weeks and then every 12 weeks after that, you will have an MRI
      or CT scan.

      If the disease appears to get worse, blood (about 3 tablespoons) will be drawn for biomarker
      testing.

      End-of-Treatment Visit:

      As soon as possible after your last dose of study drugs:

        -  You will have a physical exam.

        -  Blood (about 3 tablespoons) will be drawn for biomarker and routine tests.

      If you stopped taking the study drugs for reasons other than the disease getting worse, you
      will continue to have MRI or CT scans as described above.

      Safety Follow-Up:

      About 30 days after your End-of-Treatment visit, blood (about 1 teaspoon) will be drawn to
      check your thyroid function.

      Long Term Follow-Up:

      About every 8 weeks for the first 3 years and then every 12 weeks after that, a member of the
      study staff will contact you to ask how you are doing. This contact will take place either
      during a regularly scheduled clinic visit or by phone. Each phone call should last about 10
      minutes. If the disease gets worse, you start a new cancer treatment, withdraw from the
      study, or you cannot be reached, this contact will stop.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + EpacadostatExperimentalParticipants receive Pembrolizumab by vein over about 30 minutes on Day 1 of each 21 day cycle. Participants take 2 Epacadostat pills by mouth every day while on study. Tablets should be taken about 12 hours apart (1 morning dose, 1 evening dose) at the same time each day.
  • Pembrolizumab
  • Epacadostat

Eligibility Criteria

        Inclusion Criteria:

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

          2. Be >/= 18 years of age on day of signing informed consent.

          3. Have received at least one prior therapy for metastatic disease.

          4. Patients with HRD identified by one of the following criteria: a)Tested positive for
             BRCA 1 or 2 germline deleterious mutation, b)Previously identified genetic aberrations
             that are associated with HRD [e.g., somatic BRCA mutation, PALB2, Fanconi Anemia gene
             or RAD51 mutations], c)Patients with somatic ATM loss as identifiable with
             immunohistochemistry or with ATM mutation, d) PDAC patients with family history of 2
             or more first-degree relatives with BRCA-associated cancers (stomach, breast, ovary)
             or 1 or more first-degree relative with PDAC

          5. Have measurable disease based on RECIST 1.1 or at least one site of disease must be
             uni-dimensionally measurable as per RECIST 1.1. All radiology studies must be
             performed within 28 days prior to registration

          6. Patients must have an archival sample of tumor or metastatic site core biopsy to be
             eligible.

          7. Have a performance status of 0 or 1 on the ECOG Performance Scale.

          8. Demonstrate adequate organ function, all screening labs should be performed within 10
             days of treatment initiation: a) Hematological: Absolute neutrophil count (ANC) >/=
             1.5×109/L, platelet count >/= 100×109/L, and hemoglobin >/= 9 g/dl without transfusion
             or EPO dependency (within 7 days of assessment). b) Renal: If serum creatinine
             concentration >/= 1.5× upper limit of normal (ULN), then estimated creatinine
             clearance must be >/= 60 mL/min for subject with creatinine levels > 1.5 ×
             institutional ULN. c) Hepatic: total bilirubin </= 1.5× ULN (≤ 3 X ULN if a exists a
             history of Gilbert syndrome alanine) or Direct bilirubin >/= ULN for subjects with
             total bilirubin levels > 1.5 ULN, aminotransferase (ALT) and aspartate
             aminotransferase (AST) </= 2.5× ULN and albumin >/= 3 mg/dL. Creatinine clearance
             should be calculated per institutional standard.

          9. Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

         10. Female subjects of childbearing potential must be willing to use an adequate method of
             contraception, 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.

         11. Male subjects of childbearing potential must agree to use an adequate method of
             contraception. Contraception, starting with the first dose of study therapy through
             120 days after the last dose of study therapy. Note: Abstinence is acceptable if this
             is the usual lifestyle and preferred contraception for the subject.

        Exclusion Criteria:

          1. 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.

          2. For screening ECGs, exclude patients with a QTcF > 480ms, or JTc > 340ms for those
             with an intraventricular conduction delay. If the screening ECG has a QTcF > 480ms,
             eligibility can be confirmed if the average of 3 ECGs done 5 minutes apart have an
             average QTcF < 480 ms.

          3. 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.

          4. Has a known history of active TB (Bacillus Tuberculosis)

          5. Hypersensitivity to pembrolizumab or epacadostat or any of their excipients.

          6. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
             Day 1 or who has not recovered (i.e., </= Grade 1 or at baseline) from adverse events
             due to agents administered more than 4 weeks earlier.

          7. 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: Subjects
             with </= Grade 2 neuropathy 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.

          8. Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          9. 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.

         10. Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

         11. Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis.

         12. Has an active infection requiring systemic therapy.

         13. 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.

         14. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         15. 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.

         16. Has received prior therapy with an anti-IDO-1 agent.

         17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

         19. Has received a live vaccine within 30 days of planned start of study therapy.

         20. Has ascites that requires frequent paracentesis or a pleural effusion that requires
             repeated thoracentesis.

         21. Has arterial vascular involvement.

         22. Has received monoamine oxidase inhibitors within 21 days prior to starting study

         23. Has any history of Serotonin Syndrome after receiving serotonergic drugs.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Best Objective Response of Epacadostat in Combination With Pembrolizumab in Advanced Pancreatic Cancer With Chromosomal Instability/ Homologous Recombination Repair Deficiency (HRD)
Time Frame:Every 9 weeks from the start of treatment for the first 36 weeks up to 1 year
Safety Issue:
Description:Best objective response achieved during the treatment as assessed on CT/MRI imaging by RECIST criteria.

Secondary Outcome Measures

Measure:Disease Control Rate of Epacadostat in Combination With Pembrolizumab in Advanced Pancreatic Cancer With Chromosomal Instability/ Homologous Recombination Repair Deficiency (HRD)
Time Frame:Start of drug combination up to 6 months
Safety Issue:
Description:Disease control rate defined as the percentage of subjects with a RECIST response of stable disease for over 6 months, partial response or complete response.
Measure:Progression free survival (PFS)
Time Frame:Baseline up to 1 year
Safety Issue:
Description:PFS) defined as the time from the date of study entry to the date of progression or to the date of death from any cause, whichever occurred first.
Measure:Overall Survival (OS) of Epacadostat in Combination With Pembrolizumab in Advanced Pancreatic Cancer With Chromosomal Instability/ Homologous Recombination Repair Deficiency (HRD)
Time Frame:Baseline up to 1 year
Safety Issue:
Description:OS) defined as the time from date of study entry to the date of death from any cause or to the date of last follow-up if patients are alive.
Measure:CA 19-9 Clinical Response of Epacadostat in Combination With Pembrolizumab in Advanced Pancreatic Cancer With Chromosomal Instability/ Homologous Recombination Repair Deficiency (HRD)
Time Frame:Baseline and at 9 weeks of treatment
Safety Issue:
Description:The CA 19-9 clinical response defined as the percentage reduction before and after 9 weeks of treatment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Pancreatic Adenocarcinoma
  • Homologous recombination repair deficiency
  • HRD
  • Pembrolizumab
  • Keytruda
  • MK-3475
  • SCH-900475
  • Epacadostat
  • INCB024360

Last Updated

February 26, 2018