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Pembrolizumab and Epacadostat in Patients With Thymic Carcinoma

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ClinicalTrials.gov Identifier: NCT02364076
Recruitment Status : Active, not recruiting
First Posted : February 16, 2015
Last Update Posted : November 30, 2018
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Incyte Corporation
Information provided by (Responsible Party):
Georgetown University

Tracking Information
First Submitted Date  ICMJE February 10, 2015
First Posted Date  ICMJE February 16, 2015
Last Update Posted Date November 30, 2018
Actual Study Start Date  ICMJE March 2015
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2015)
Response rate [ Time Frame: 24 months ]
complete response plus partial response as determined by RECIST 1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02364076 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2017)
  • Progression-free survival [ Time Frame: 42 months ]
    Time between start of treatment and tumor progression or death
  • Overall survival [ Time Frame: 42 months ]
    Time between start of treatment and death
  • Tolerability as measured by Adverse events and serious adverse events experienced by subjects [ Time Frame: 24 months ]
    Adverse events and serious adverse events experienced by subjects
Original Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2015)
  • Progression-free survival [ Time Frame: 24 months ]
    Time between start of treatment and tumor progression or death
  • Overall survival [ Time Frame: 30 months ]
    Time between start of treatment and death
  • Tolerability as measured by Adverse events and serious adverse events experienced by subjects [ Time Frame: 24 months ]
    Adverse events and serious adverse events experienced by subjects
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pembrolizumab and Epacadostat in Patients With Thymic Carcinoma
Official Title  ICMJE Pembrolizumab (MK-3475) and Epacadostat (INCB024360) in Thymic Carcinomas
Brief Summary This is a non-randomized clinical trial in patients with thymic carcinomas who failed prior systemic therapy. All subjects will receive pembrolizumab and epacadostat treatment in three week cycles until unacceptable toxicity, death, progressive disease or withdrawal.
Detailed Description The amended phase II study of pembrolizumab and epacadostat is for thymic carcinoma patients who recurred after at least one prior chemotherapy regimen. The primary endpoint is response rate; secondary endpoints are Progression-Free Survival, Overall Survival and treatment tolerability. Responses will be assessed according to RECIST 1.1; progression-free survival is defined as time between start of treatment and tumor progression or death; survival is the time between start of treatment and death. Furthermore exploratory studies will be performed on archival tumor material (PDL-1 expression, next-generation sequencing), and fresh biopsies (culturing; next-generation sequencing).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Thymic Carcinoma
  • Thymus Neoplasms
  • Thymus Cancer
Intervention  ICMJE
  • Drug: Pembrolizumab
    Administration of 200 mg MK-3475 once every 3 weeks
    Other Names:
    • Keytruda
    • MK-3475
  • Drug: Epacadostat
    100mg taken by mouth twice daily
    Other Name: INCB024360
Study Arms  ICMJE Experimental: Pembrolizumab and Epacadostat
Pembrolizumab 200 mg intravenously every 3 weeks Epacadostat 100mg by mouth taken daily
Interventions:
  • Drug: Pembrolizumab
  • Drug: Epacadostat
Publications * Giaccone G, Kim C, Thompson J, McGuire C, Kallakury B, Chahine JJ, Manning M, Mogg R, Blumenschein WM, Tan MT, Subramaniam DS, Liu SV, Kaplan IM, McCutcheon JN. Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. Lancet Oncol. 2018 Mar;19(3):347-355. doi: 10.1016/S1470-2045(18)30062-7. Epub 2018 Jan 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 28, 2018)
45
Original Estimated Enrollment  ICMJE
 (submitted: February 13, 2015)
17
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologic confirmation of thymic carcinoma (WHO Classification, See Appendix 12.1)
  2. Advanced disease (Masaoka staging, See Appendix 12.2) not amenable to curative treatment.
  3. At least 1 prior line of chemotherapy.
  4. Progression of disease must be documented prior to study entry.
  5. Absence of any autoimmune syndrome typically associated with thymomas but not thymic carcinomas (myasthenia gravis, pure red cell aplasia, etc.).
  6. Be willing and able to provide written informed consent/assent for the trial.
  7. Be at least 18 years of age on day of signing informed consent.
  8. Have measurable disease based on RECIST 1.1.
  9. Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion.
  10. Have a performance status of 0 or 1 on the ECOG Performance Scale (See Appendix 12.3).
  11. Demonstrate adequate organ function
  12. 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.
  13. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  14. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

  1. Has disease which is amenable to radical treatment with surgery or radiation or a combination of treatments.
  2. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
  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 had a prior monoclonal antibody 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.
  5. 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.
  6. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
  7. 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.
  8. Has an active automimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
  9. Has evidence of interstitial lung disease
  10. Has a history of non-infectious pneumonitis that required steroids, or has a history of active pneumonitis.
  11. Has an active infection requiring systemic therapy.
  12. 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.
  13. Has known hypersensitivity to pembrolizumab (MK-3475) or its formulation.
  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-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  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 prior to the first dose of trial treatment.
  20. Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
  21. Screening ECG with QTc interval > 480 milliseconds (corrected by Fridericia). In the event that a single QTc is >480 msec, the subject may enroll if the average QTc for 3 ECGs is < 480 msec.
  22. Prior receipt of an IDO inhibitor.
  23. Receipt of MAOIs within 21 days before first dose of study treatment.
  24. History of serotonergic syndrome.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02364076
Other Study ID Numbers  ICMJE 2014-1315
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Georgetown University
Study Sponsor  ICMJE Georgetown University
Collaborators  ICMJE
  • Merck Sharp & Dohme Corp.
  • Incyte Corporation
Investigators  ICMJE
Principal Investigator: Giuseppe Giaccone, MD PhD Georgetown University
PRS Account Georgetown University
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP