Head and Neck Squamous Cell CarcinomaPhase 2ORKANCT03463161
Epacadostat and Pembrolizumab in Patients With Head and Neck Cancer That Have Failed Prior Immunotherapy
A Phase 2 study testing Pembrolizumab and Epacadostat in people with Head and Neck Squamous Cell Carcinoma and Head and Neck Cancer, run by University of Chicago at 1 site in United States.
Trial summary
Study to determine response rate of the combination of pembrolizumab plus epacadostat in patients with head and neck cancers that have received prior immunotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma, Head and Neck Cancer
- What is being tested?
- Pembrolizumab and Epacadostat
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Mar 2018to 4 Dec 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Squamous cell carcinoma of the head and neck (which cannot be surgically removed and not amenable to curative intent therapy)
- Meet criteria for either the Acquired Resistance OR the Suboptimal Benefit Group * Acquired Resistance defined as (i and ii must both be met): i. Prior benefit from anti-PD-1/PD-L1 therapy defined as a) prior response, and/or b) ≥5 months of stable disease (SD). Intervening therapies are allowed.
- Progressive Disease (PD) on recent scans
- Suboptimal Benefit is defined as (i and ii must both be met): i. Prolonged stable disease ≥5 months OR Suboptimal response (>10% \& <50% shrinkage per RECIST at any evaluation timepoint) ii. Ongoing stable disease on recent scans iii. Last treatment with an anti-PD-1/PD-L1 agent within 6 weeks prior to starting protocol treatment
- Availability of stored tumor tissue OR new tumor biopsy Archival tissue for PD-L1 staining (alternatively a new biopsy (core) at baseline can be used). A minimum of 10 slides is required (unless approval from the PI is obtained)
- Measurable disease
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- Known human papillomavirus (HPV) status
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Be willing and able to provide written informed consent for the trial.
- Aged 18 years or older
- Demonstrate reasonable organ function
- Women of childbearing potential should have a negative urine or serum pregnancy test
- Women 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
- Males should agree to use an adequate method of birth control starting with the first dose of study therapy through 120 days after the last dose of study medication
Who cannot join
- Currently participating and receiving treatment in a research study or has participated in a study of an investigational therapy and received study therapy or used an investigational device within 2 weeks of the first dose of treatment on this study
- 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.
- Known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab, epacadostat or any of its excipients.
- Has received prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study Day 1, or targeted small molecule 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 agents administered more than 4 weeks earlier.
- Has not recovered from prior surgery, chemotherapy or radiation therapy from adverse events due to a previous treatment/ administered agent (i.e., ≤ Grade 1 or return to baseline prior to treatment).
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- Note: Participants with ≤ Grade 2 neuropathy, any grade hearing loss or tinnitus, or typical side effects from radiotherapy 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 or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or any tumors that are not likely to influence live expectancy in the subsequent 3 years without active treatment (e.g. low grade prostate cancer in absence of therapy).
- Has known active (=growing) central nervous system (CNS) metastases and/or carcinomatous meningitis. Radiation or resected brain metastasis are acceptable if clinically stable.
- 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.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Warfarin use, even if low dose warfarin is not acceptable. However, other anti-coagulants (e.g. aspirin, enoxaparin and heparin derivatives, thrombin inhibitors, etc) are acceptable.
- 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 IDO inhibiting agent.
- 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.
- Has received MAO-inhibitors (MAOI) or drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening.
- History of Serotonin Syndrome after receiving serotonergic drugs.
- History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. Screening QTc interval > 470 milliseconds is excluded.
- Use of any UGT1A9 inhibitor from screening through follow-up period, including the following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid. See Section 5.11 for more details.
- History of organ transplant that requires use of immunosuppressives.
- Any condition that would jeopardize the safety of the subject or compliance with the Protocol.
- Clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Chicago Medical Center
Chicago, Illinois, 60637
About this study
Official title: A Phase II Study of Epacadostat + Pembrolizumab in Head and Neck Cancer Patients, Who Failed Prior PD-1/PD-L1 Therapy
Study to determine response rate of the combination of pembrolizumab plus epacadostat in patients with head and neck cancers that have received prior immunotherapy.
- Being tested
- Pembrolizumab, Epacadostat
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda, MK3476
Pembrolizumab (200mg/kg) given by intravenous infusion every 3 weeks.
EpacadostatDrug
Also called INCB024360
Epacadostat (100mg) taken by mouth twice a day.
| Study group | Role | What they receive |
|---|---|---|
| Acquired Resistance Group | Experimental | Participants that have benefited from prior treatment with immunotherapy. Defined as response to prior treatment and/or stable disease lasting at least 5 months and disease worsening seen on most recent imaging.
Participants will receive Pembrolizumab and Epacadostat. Receives: Drug: Pembrolizumab; Drug: Epacadostat |
| Suboptimal Benefit Group | Experimental | Participants that have not benefited from prior treatment with immunotherapy. Defined as stable disease lasting at least 5 months or suboptimal response (11-49% shrinkage of tumors). Disease continues to be stable on most recent imaging.
Participants will receive Pembrolizumab and Epacadostat. Receives: Drug: Pembrolizumab; Drug: Epacadostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
Rate of clinical disease response (tumor shrinkage) as seen on imaging.
Measured: up to 18 months
Secondary outcomes (3)
Progression Free Survival
Number of patients that have not had disease worsening across both study groups.
Measured: 1 year
Overall Survival
Number of patients surviving across both study groups.
Measured: 1 year
Side Effects
Number of patients with side effect. Summary of side effects by type is provided in adverse events section below.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2018
- Study start23 Mar 2018
- Primary completion4 Dec 2018
- Study completion4 Dec 2018
Why it stopped: Study stopped early due to investigator conflict of interest.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be assigned to one of 2 study groups based on response to prior therapy.
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tanguy Seiwert, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03463161
- Sponsor's protocol ID
- IRB17-1539
- Acronym
- ORKA
- Status last verified
- Jan 2020
- First submitted
- 6 Mar 2018
- Last updated
- 27 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Epacadostat + Pembrolizumab in Head and Neck Cancer Patients, Who Failed Prior PD-1/PD-L1 Therapy
- ClinicalTrials.gov ID
- NCT03463161
- Acronym / sponsor ID
- ORKA / IRB17-1539
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study stopped early due to investigator conflict of interest.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 23 Mar 2018 (actual)
- Primary completion
- 4 Dec 2018 (actual)
- Study completion
- 4 Dec 2018 (actual)
- First posted
- 13 Mar 2018 (actual)
- Results
- Posted 27 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study to determine response rate of the combination of pembrolizumab plus epacadostat in patients with head and neck cancers that have received prior immunotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will be assigned to one of 2 study groups based on response to prior therapy.
| Arm | Type | Receives |
|---|---|---|
| Acquired Resistance Group | Experimental | Drug: Pembrolizumab, Drug: EpacadostatParticipants that have benefited from prior treatment with immunotherapy. Defined as response to prior treatment and/or stable disease lasting at least 5 months and disease worsening seen on most recent imaging. Participants will receive Pembrolizumab and Epacadostat. |
| Suboptimal Benefit Group | Experimental | Drug: Pembrolizumab, Drug: EpacadostatParticipants that have not benefited from prior treatment with immunotherapy. Defined as stable disease lasting at least 5 months or suboptimal response (11-49% shrinkage of tumors). Disease continues to be stable on most recent imaging. Participants will receive Pembrolizumab and Epacadostat. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Squamous cell carcinoma of the head and neck (which cannot be surgically removed and not amenable to curative intent therapy)
- Meet criteria for either the Acquired Resistance OR the Suboptimal Benefit Group * Acquired Resistance defined as (i and ii must both be met): i. Prior benefit from anti-PD-1/PD-L1 therapy defined as a) prior response, and/or b) ≥5 months of stable disease (SD). Intervening therapies are allowed.
- Progressive Disease (PD) on recent scans
- Suboptimal Benefit is defined as (i and ii must both be met): i. Prolonged stable disease ≥5 months OR Suboptimal response (>10% \& <50% shrinkage per RECIST at any evaluation timepoint) ii. Ongoing stable disease on recent scans iii. Last treatment with an anti-PD-1/PD-L1 agent within 6 weeks prior to starting protocol treatment
- Availability of stored tumor tissue OR new tumor biopsy Archival tissue for PD-L1 staining (alternatively a new biopsy (core) at baseline can be used). A minimum of 10 slides is required (unless approval from the PI is obtained)
Key exclusion criteria (27 listed)
- Currently participating and receiving treatment in a research study or has participated in a study of an investigational therapy and received study therapy or used an investigational device within 2 weeks of the first dose of treatment on this study
- 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.
- Known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab, epacadostat or any of its excipients.
- Has received prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study Day 1, or targeted small molecule 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 agents administered more than 4 weeks earlier.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: Keytruda, MK3476Pembrolizumab (200mg/kg) given by intravenous infusion every 3 weeks. | Drug | Acquired Resistance Group, Suboptimal Benefit Group |
| EpacadostatAlso: INCB024360Epacadostat (100mg) taken by mouth twice a day. | Drug | Acquired Resistance Group, Suboptimal Benefit Group |
Primary outcome
Response Rate
Time frame: up to 18 months
Rate of clinical disease response (tumor shrinkage) as seen on imaging.
3 secondary outcomes
Progression Free Survival
Time frame: 1 year
Overall Survival
Time frame: 1 year
Side Effects
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tanguy Seiwert, MD principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and Epacadostat in people with Head and Neck Squamous Cell Carcinoma and Head and Neck Cancer, run by University of Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Rate (time frame: up to 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2020.