Gastrointestinal Stromal TumorsPhase 2NCT03291054
Epacadostat and Pembrolizumab in Patients With GIST
A Phase 2 study testing Pembrolizumab and Epacadostat in people with Gastrointestinal Stromal Tumors, run by Columbia University at 2 sites in United States.
Trial summary
Primary objective is to assess the efficacy of combined Indoleamine 2,3-dioxygenase (IDO) and PD-1 inhibition in a single arm phase II trial of epacadostat and pembrolizumab in patients with advanced imatinib-refractory GIST, using a primary endpoint of overall response rate. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors
- 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
- 1 participants
- Where
- 2 sitesUnited States
- Study dates
- 28 Feb 2018to 19 Aug 2020
- 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
- Histologically confirmed diagnosis of GIST.
- Unresectable or metastatic GIST
- Allowable prior therapies:
- Subjects must have had clinical or radiographic progression on imatinib. Those who were taken off of imatinib for intolerance must have progressed on at least one other tyrosine kinase inhibitor (TKI).
- Subjects must have received ≥ 1 prior systemic therapy (including imatinib). A maximum of 4 prior therapies for metastatic disease are allowed.
- Male or female subjects, age 18 years or older.
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- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Life expectance of ≥ 3 months.
- Laboratory and medical history parameters within the following Protocol-defined range.
- All screening laboratory tests should be performed within 28 days of treatment initiation and must be independent of hematopoietic growth factor support.
- Absolute neutrophil count ≥ 1.5 x 109/L.
- Platelets ≥ 100 x 109/L.
- Hemoglobin ≥ 9 g/dL (transfusion is acceptable to meet this criteria)
- Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) OR calculated creatinine clearance ≥ 50 mL/min for subjects with creatinine levels > 1.5 x institutional ULN.
- Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase ≤ 2.5 x ULN, or ≤ 5 x ULN in subjects with liver metastases.
- Total bilirubin ≤ 1.5 x ULN
- o Note: patients with hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (eg, Gilbert syndrome) will be eligible at the discretion of the principal investigator.
- International normalized ratio (INR) or prothrombin time (PT) < 1.5x ULN unless subject is receiving anticoagulation therapy as long as PT or INR is within therapeutic range of intended use of anticoagulant.
- Activated partial thromboplastin time (aPTT) < 1.5 x ULN unless subject is receiving anticoagulant therapy, as long as PTT is within therapeutic range of intended use of anticoagulants.
- Presence of baseline measureable disease by RECIST v1.1 for solid tumors, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan, MRI, or calipers by clinical exam. (See Section 15.4 for the evaluation of measurable disease).
- The effects of pembrolizumab and epacadostat on the developing human fetus are unknown, and thus female subjects of childbearing potential (defined as women who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy, and are not postmenopausal (defined as ≥ 12 months of amenorrhea)) must have a negative pregnancy test at screening and must agree to use adequate contraception (complete abstinence, or two methods of birth control (Appendix B)) prior to study entry and until at least 4 months after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Fertile men must also agree to use adequate contraception (2 barrier methods or abstinence) during the study and for up to 4 months after the last dose of study drug.
- All subjects must agree to pre- and on-treatment tumor biopsies. 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. Use of outside archived tumor tissue for a baseline biopsy is not permitted.
- Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.
Who cannot join
- Treatment with chemotherapy (not including Tyrosine Kinase Inhibitors) or radiotherapy within 4 weeks (6 weeks from nitrosoureas or mitomycin C), or treatment with monoclonal antibody therapy within 4 weeks prior to start of study treatment. Note: No minimum washout period is required for tyrosine kinase inhibitor therapy (eg, imatinib or sunitinib).
- Patients must have recovered from adverse events (greater than grade 1) due to prior anticancer therapy, except for stable chronic toxicities such as alopecia.
- Participation in any other clinical study with investigational drug received within 28 days or 5 half lives (whichever is longer) before first dose.
- Subjects who have received prior anti-PD-1 or anti-PD-L1 antibody, or an IDO inhibitor.
- Subjects who have received experimental vaccines or other immune therapies should be discussed with the principal investigator to confirm eligibility.
- Any prior ≥ Grade 3 immune-related adverse event (irAE) while receiving immunotherapy, or any unresolved irAE > grade 1.
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- Subjects receiving immunologically based treatment for any reason, including chronic steroids or prednisone (at dose >10 mg/day of prednisone) within 14 day prior to first study treatment. Inhaled or topical steroids or systemic steroids (at dose ≤10 mg/day of prednisone) is permitted.
- Subjects with any active or inactive autoimmune process (eg, rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease) or who are receiving systemic therapy for an autoimmune disease. Exceptions include vitiligo, hypothyroidism controlled on hormone replacement, type I diabetes, Grave's disease, adrenal insufficiency on stable replacement doses of steroids (prednisone ≤10 mg/day or equivalent), or with principal investigator approval.
- No prior organ allograft or allogenic bone marrow transplantation.
- History of (noninfectious) pneumonitis that require steroids or current pneumonitis.
- A diagnosis of another active malignancy with the following exceptions: basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, isolated elevation of prostate-specific antigen, indolent secondary malignancies not requiring active therapy, or with the approval of the principal investigator. Subjects with a completely treated prior malignancy and no evidence of disease for ≥ 2 years are eligible.
- Subjects with known active hepatitis B (HBV) or hepatitis C (HCV) infection as defined by the following (Hepatitis screening studies are required:
- Positive test for hepatitis B surface antigen
- Positive test for hepatitis C antibody and/ or hepatitis C quantitative viral load (Note: Subjects with a positive hepatitis C antibody and negative quantitative hepatitis C polymerase chain reaction (PCR) viral load are eligible)
- Subjects with a known history of HIV, including patients with controlled disease on antiretroviral therapy. HIV testing is not required as part of screening for this study.
- Subjects receiving monoamine oxidase (MAO) inhibitors within 21 days of study enrollment (epacadostat increases serotonin levels, theoretically increasing the risk of serotonin syndrome, although this has not been reported in any ongoing clinical studies to date).
- Any history of serotonin syndrome (SS) after receiving 1 or more serotonergic drugs.
- Current pregnancy or breast feeding. Pregnant women are excluded from this study because the teratogenicity of epacadostat and pembrolizumab are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab and/or epacadostat, breastfeeding should be discontinued in all female subjects.
- Receipt of live attenuated vaccines (including, but not limited to: intranasal influenza vaccine (FluMist), measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine) within 30 days before the first dose of study treatment.
- Concurrent use of any medication that is an inhibitor of UGT1A9 during the screening or treatment period.
- Major surgical procedure or significant traumatic injury within 14 days of initiating study drug or anticipation of the need for major surgery during the study.
- Inability to swallow capsules, or refractory nausea and vomiting, malabsorption, an external biliary shunt, or significant bowel resection that would preclude adequate absorption.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active liver disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- History of current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, or interfere with the subject's participation for the full duration of the study.
- Known allergy or reaction to any component of either study drug formulation.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
U-M Comprehensive Cancer Center
Ann Arbor, Michigan, 48109-0944
Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: A Phase II Study of Epacadostat and Pembrolizumab in Patients With Imatinib Refractory Advanced Gastrointestinal Stromal Tumors
Primary objective is to assess the efficacy of combined Indoleamine 2,3-dioxygenase (IDO) and PD-1 inhibition in a single arm phase II trial of epacadostat and pembrolizumab in patients with advanced imatinib-refractory GIST, using a primary endpoint of overall response rate.
Secondary objectives are to evaluate the progression free survival (PFS), the overall survival (OS), the response rate and to evaluate the safety and tolerability of combined epacadostat and pembrolizumab treatment.
The investigator hypothesizes that treatment with epacadostat and pembrolizumab will increase the response rate compared to what has been historically achieved with salvage tyrosine kinase inhibitors.
Read the detailed description
While targeted therapy with imatinib has significantly improved survival for patients with inoperable and metastatic gastrointestinal stromal tumors (GIST), the majority will eventually progress after a median of 20-26 months. Standard second-line treatment with sunitinib has a response rate of 7%, and third-line treatment with regorafenib has a response rate of only 5%. More effective treatments for imatinib-refractory GIST are needed.
This study aims to assess the efficacy of combined IDO and PD-1 inhibition with epacadostat (IDO inhibitor) and pembrolizumab (anti-PD-1 antibody) in patients with imatinib-refractory GIST.
- Conditions
- Gastrointestinal Stromal Tumors
- Being tested
- Pembrolizumab, Epacadostat
- Keywords
- Gastrointestinal Stromal Tumors, GIST, Pembrolizumab, Epacadostat, Columbia
- Medical subject headings
- Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda, Anti-PD-1 antibody
Subjects will receive pembrolizumab 200 mg (flat dose) IV every 3 weeks on day 1 of a 21 day cycle.
EpacadostatDrug
Also called INCB024360, IDO inhibitor
Epacadostat will be dosed at 100 mg PO twice a day (BID) daily. Doses should be taken twice daily, in the morning and evening, approximately 12 hours apart, without regard to food.Doses will be self-administered, except on Cycle 2 Day 1, when the morning dose will be given at the study site clinic. Subjects will be required to keep a pill diary that will be provided to them.
| Study group | Role | What they receive |
|---|---|---|
| Epacadostat and pembrolizumab | Experimental | Subjects will receive epacadostat and pembrolizumab Receives: Drug: Pembrolizumab; Drug: Epacadostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
The primary endpoint is the overall response rate as defined as the best response using RECIST v1.1 criteria. A standard way to measure how well a cancer patient responds to treatment. It is based on whether tumors shrink, stay the same, or get bigger. To use RECIST, there must be at least one tumor that can be measured on x-rays, CT scans, or MRI scans. The types of response a patient can have are a complete response (CR), a partial response (PR), progressive disease (PD), and stable disease (SD). Also called Response Evaluation Criteria In Solid Tumors.
Measured: within the first 24 weeks of the start of study therapy
Secondary outcomes (1)
Overall Survival
The length of time from the start of treatment that patients diagnosed with the disease are still alive.
Measured: time from registration up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2017
- Study start28 Feb 2018
- Primary completion19 Aug 2020
- Study completion19 Aug 2020
Why it stopped: Study ended prematurely at the request of the funding sponsor.
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 Gastrointestinal Stromal TumorsStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Richard D Carvajal, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03291054
- Sponsor's protocol ID
- AAAR1581
- Status last verified
- May 2024
- First submitted
- 20 Sep 2017
- Last updated
- 11 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Epacadostat and Pembrolizumab in Patients With Imatinib Refractory Advanced Gastrointestinal Stromal Tumors
- ClinicalTrials.gov ID
- NCT03291054
- Acronym / sponsor ID
- AAAR1581
- Conditions
- Gastrointestinal Stromal Tumors
- Keywords
- Gastrointestinal Stromal Tumors, GIST, Pembrolizumab, Epacadostat, Columbia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study ended prematurely at the request of the funding sponsor.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 28 Feb 2018 (actual)
- Primary completion
- 19 Aug 2020 (actual)
- Study completion
- 19 Aug 2020 (actual)
- First posted
- 25 Sep 2017 (actual)
- Results
- Posted 11 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary objective is to assess the efficacy of combined Indoleamine 2,3-dioxygenase (IDO) and PD-1 inhibition in a single arm phase II trial of epacadostat and pembrolizumab in patients with advanced imatinib-refractory GIST, using a primary endpoint of overall response rate.
Secondary objectives are to evaluate the progression free survival (PFS), the overall survival (OS), the response rate and to evaluate the safety and tolerability of combined epacadostat and pembrolizumab treatment.
The investigator hypothesizes that treatment with epacadostat and pembrolizumab will increase the response rate compared to what has been historically achieved with salvage tyrosine kinase inhibitors.
Detailed description
While targeted therapy with imatinib has significantly improved survival for patients with inoperable and metastatic gastrointestinal stromal tumors (GIST), the majority will eventually progress after a median of 20-26 months. Standard second-line treatment with sunitinib has a response rate of 7%, and third-line treatment with regorafenib has a response rate of only 5%. More effective treatments for imatinib-refractory GIST are needed.
This study aims to assess the efficacy of combined IDO and PD-1 inhibition with epacadostat (IDO inhibitor) and pembrolizumab (anti-PD-1 antibody) in patients with imatinib-refractory GIST.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Epacadostat and pembrolizumab | Experimental | Drug: Pembrolizumab, Drug: EpacadostatSubjects will receive epacadostat and pembrolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Histologically confirmed diagnosis of GIST.
- Unresectable or metastatic GIST
- Allowable prior therapies:
- Male or female subjects, age 18 years or older.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Key exclusion criteria (25 listed)
- Treatment with chemotherapy (not including Tyrosine Kinase Inhibitors) or radiotherapy within 4 weeks (6 weeks from nitrosoureas or mitomycin C), or treatment with monoclonal antibody therapy within 4 weeks prior to start of study treatment. Note: No minimum washout period is required for tyrosine kinase inhibitor therapy (eg, imatinib or sunitinib).
- Patients must have recovered from adverse events (greater than grade 1) due to prior anticancer therapy, except for stable chronic toxicities such as alopecia.
- Participation in any other clinical study with investigational drug received within 28 days or 5 half lives (whichever is longer) before first dose.
- Subjects who have received prior anti-PD-1 or anti-PD-L1 antibody, or an IDO inhibitor.
- Subjects who have received experimental vaccines or other immune therapies should be discussed with the principal investigator to confirm eligibility.
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, Anti-PD-1 antibodySubjects will receive pembrolizumab 200 mg (flat dose) IV every 3 weeks on day 1 of a 21 day cycle. | Drug | Epacadostat and pembrolizumab |
| EpacadostatAlso: INCB024360, IDO inhibitorEpacadostat will be dosed at 100 mg PO twice a day (BID) daily. Doses should be taken twice daily, in the morning and evening, approximately 12 hours apart, without regard to food.Doses will be self-administered, except on Cycle 2 Day 1, when the morning dose will be given at the study site clinic. Subjects will be required to keep a pill diary that will be provided to them. | Drug | Epacadostat and pembrolizumab |
Primary outcome
Overall Response Rate
Time frame: within the first 24 weeks of the start of study therapy
The primary endpoint is the overall response rate as defined as the best response using RECIST v1.1 criteria. A standard way to measure how well a cancer patient responds to treatment. It is based on whether tumors shrink, stay the same, or get bigger. To use RECIST, there must be at least one tumor that can be measured on x-rays, CT scans, or MRI scans. The types of response a patient can have are a complete response (CR), a partial response (PR), progressive disease (PD), and stable disease (SD). Also called Response Evaluation Criteria In Solid Tumors.
1 secondary outcome
Overall Survival
Time frame: time from registration up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Richard D Carvajal, MD principal investigator
Columbia University
2 sites 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 Gastrointestinal Stromal Tumors, run by Columbia University at 2 sites 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 24 inclusion and 25 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 11 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 11 Jun 2024). 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?
Overall Response Rate (time frame: within the first 24 weeks of the start of study therapy). 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 11 Jun 2024.