Pembrolizumab and Epacadostat in Patients With Thymic Carcinoma
Primary Purpose
Thymic Carcinoma, Thymus Neoplasms, Thymus Cancer
Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pembrolizumab
Epacadostat
Sponsored by
About this trial
This is an interventional treatment trial for Thymic Carcinoma focused on measuring Pembrolizumab, Epacadostat
Eligibility Criteria
Inclusion Criteria:
- Histologic confirmation of thymic carcinoma (WHO Classification, See Appendix 12.1)
- Advanced disease (Masaoka staging, See Appendix 12.2) not amenable to curative treatment.
- At least 1 prior line of chemotherapy.
- Progression of disease must be documented prior to study entry.
- Absence of any autoimmune syndrome typically associated with thymomas but not thymic carcinomas (myasthenia gravis, pure red cell aplasia, etc.).
- Be willing and able to provide written informed consent/assent for the trial.
- Be at least 18 years of age on day of signing informed consent.
- Have measurable disease based on RECIST 1.1.
- Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion.
- Have a performance status of 0 or 1 on the ECOG Performance Scale (See Appendix 12.3).
- Demonstrate adequate organ function
- 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.
- 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.
- 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:
- Has disease which is amenable to radical treatment with surgery or radiation or a combination of treatments.
- 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.
- 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.
- 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.
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.
- 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.
- 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.
- 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.
- Has evidence of interstitial lung disease
- Has a history of non-infectious pneumonitis that required steroids, or has a history of active 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 hypersensitivity to pembrolizumab (MK-3475) or its formulation.
- 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, 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).
- 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 prior to the first dose of trial treatment.
- Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
- 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.
- Prior receipt of an IDO inhibitor.
- Receipt of MAOIs within 21 days before first dose of study treatment.
- History of serotonergic syndrome.
Sites / Locations
- Georgetown Lombardi Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pembrolizumab and Epacadostat
Arm Description
Pembrolizumab 200 mg intravenously every 3 weeks Epacadostat 100mg by mouth taken daily
Outcomes
Primary Outcome Measures
Response Rate
To measure response of all the participants to the drug at the end of the study.
Secondary Outcome Measures
Progression-free Survival
Time between start of treatment and tumor progression or death
Overall Survival
Time between start of treatment and death
Number of Participants With New-Onset Severe Adverse Events
Full Information
NCT ID
NCT02364076
First Posted
February 10, 2015
Last Updated
November 26, 2019
Sponsor
Georgetown University
Collaborators
Merck Sharp & Dohme LLC, Incyte Corporation
1. Study Identification
Unique Protocol Identification Number
NCT02364076
Brief Title
Pembrolizumab and Epacadostat in Patients With Thymic Carcinoma
Official Title
Pembrolizumab (MK-3475) and Epacadostat (INCB024360) in Thymic Carcinomas
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Unknown status
Study Start Date
March 2015 (Actual)
Primary Completion Date
June 2019 (Actual)
Study Completion Date
December 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Georgetown University
Collaborators
Merck Sharp & Dohme LLC, Incyte Corporation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thymic Carcinoma, Thymus Neoplasms, Thymus Cancer
Keywords
Pembrolizumab, Epacadostat
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pembrolizumab and Epacadostat
Arm Type
Experimental
Arm Description
Pembrolizumab 200 mg intravenously every 3 weeks Epacadostat 100mg by mouth taken daily
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, MK-3475
Intervention Description
Administration of 200 mg MK-3475 once every 3 weeks
Intervention Type
Drug
Intervention Name(s)
Epacadostat
Other Intervention Name(s)
INCB024360
Intervention Description
100mg taken by mouth twice daily
Primary Outcome Measure Information:
Title
Response Rate
Description
To measure response of all the participants to the drug at the end of the study.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
Time between start of treatment and tumor progression or death
Time Frame
24 months
Title
Overall Survival
Description
Time between start of treatment and death
Time Frame
24 months
Title
Number of Participants With New-Onset Severe Adverse Events
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologic confirmation of thymic carcinoma (WHO Classification, See Appendix 12.1)
Advanced disease (Masaoka staging, See Appendix 12.2) not amenable to curative treatment.
At least 1 prior line of chemotherapy.
Progression of disease must be documented prior to study entry.
Absence of any autoimmune syndrome typically associated with thymomas but not thymic carcinomas (myasthenia gravis, pure red cell aplasia, etc.).
Be willing and able to provide written informed consent/assent for the trial.
Be at least 18 years of age on day of signing informed consent.
Have measurable disease based on RECIST 1.1.
Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion.
Have a performance status of 0 or 1 on the ECOG Performance Scale (See Appendix 12.3).
Demonstrate adequate organ function
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.
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.
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:
Has disease which is amenable to radical treatment with surgery or radiation or a combination of treatments.
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.
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.
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.
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.
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.
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.
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.
Has evidence of interstitial lung disease
Has a history of non-infectious pneumonitis that required steroids, or has a history of active 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 hypersensitivity to pembrolizumab (MK-3475) or its formulation.
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, 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).
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 prior to the first dose of trial treatment.
Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
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.
Prior receipt of an IDO inhibitor.
Receipt of MAOIs within 21 days before first dose of study treatment.
History of serotonergic syndrome.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giuseppe Giaccone, MD PhD
Organizational Affiliation
Georgetown University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgetown Lombardi Comprehensive Cancer Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
34622229
Citation
He Y, Ramesh A, Gusev Y, Bhuvaneshwar K, Giaccone G. Molecular predictors of response to pembrolizumab in thymic carcinoma. Cell Rep Med. 2021 Sep 3;2(9):100392. doi: 10.1016/j.xcrm.2021.100392. eCollection 2021 Sep 21.
Results Reference
derived
PubMed Identifier
29395863
Citation
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.
Results Reference
derived
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Pembrolizumab and Epacadostat in Patients With Thymic Carcinoma
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