Metastatic Colorectal CancerPhase 1/2NCT03182894
Epacadostat in Combination With Pembrolizumab and Azacitidine in Subjects With Metastatic Colorectal Cancer
A Phase 1/2 study testing Epacadostat (INCB024360) in Combination with Pembrolizumab (MK-3475) and Azacitidine (VIDAZA) in people with Metastatic Colorectal Cancer, run by James J Lee at 1 site in United States.
Trial summary
Trial Design This is an open label, single-arm, phase IB/II trial to evaluate the safety, tolerability and anti-tumor efficacy of epacadostat (INCB024360) in combination with pembrolizumab (MK-3475) plus azacitidine in patients with chemo-refractory MSS mCRC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Epacadostat (INCB024360) in Combination with Pembrolizumab (MK-3475) and Azacitidine (VIDAZA)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2018to 30 Jul 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- 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.
- The diagnosis of microsatellite-stable (MSS) mCRC will be based on histologic or cytologic confirmation. The histologic or cytologic confirmation of MSS status will be based on CLIA-certified immunohistochemistry (IHC) or PCR assay.
- Have mCRC that has been previously treated with currently approved standard therapies, including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy.
- Have measurable disease based on RECIST1.1.
- At least 1 of the tumor sites must be amenable to core needle biopsy and this may not be the site of disease used to measure antitumor response.
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- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Life expectancy of at least 12 weeks.
- Demonstrate adequate organ function as defined in Table 1 (Section 3.1.9), all screening labs should be performed within 14 days of treatment initiation.
- 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 (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - 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.
- Male subjects of childbearing potential (Section 5.7.2) must agree to use an adequate method of contraception as outlined in Section 5.7.2- 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
Who cannot join
- 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 chronic systemic steroid therapy (in doses exceeding 10mg daily of prednisone equivalent) 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 4 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.
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- 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 extensive metastatic tumor burden in the liver (> 30% of liver volume) with serum albumin <3.0 g/dL.
- Has known renal tubular acidosis with serum bicarbonate <20 mEq/L.
- Has a known hypersensitivity to azacitidine or mannitol.
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or epacadostat (INCB024360) or any of their excipients.
- 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 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has a history of (non-infectious) pneumonitis that required steroids or current 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 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-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), or indoleamine 2,3-dioxygenase (IDO) inhibitor.
- 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.
- Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- Any history of serotonin syndrome after receiving 1 or more serotonergic drugs.
- Use of any monoamine oxidase inhibitor (MAOI) or drug associated with significant monoamine oxidase (MAO) inhibitory activity (listed in Tabel 4; Section 5.5) within 21 days of cycle 1 day 1.
- Use of any melatonin supplements within 21 days of cycle 1 day 1.
- Use of any UGT1A9 inhibitor, including (Section 5.5): acitretin, amitriptyline, androsterone, cyclosporine, dasatinib, diclofenac, diflunisal, efavirenz, erlotinib, estradiol (17-beta), flutamide, geftinib, gemfibrozil, glycyrrhetinic acid glycyrrhizin, imatinib, imipramine, ketoconazole, linoleic acid, mefenamic acid, mycophenolic acid, niflumic acid, nilotinib, phenobarbital, phenylbutazone, phenytoin, probenecid, propofol, quinidine, ritonavir, Sorafenib, sulfinpyrazone, valproic acid, and verapamil within 21 days of cycle 1 day 1.
- Note: Propofol, when used for short-term sedation during surgical/biopsy procedures, is allowed after consultation with the protocol chair or sponsor. Please check the detailed instruction for the use of propofol in Section 5.5)
- Presence of a gastrointestinal condition that may affect drug absorption.
- History or presence of an abnormal electrocardiogram (ECG) which, in the investigator's opinion, is clinically meaningful. Subjects with screening QTc interval > 480 ms are excluded. For subjects with an intraventricular conduction delay (QRS interval 120 ms), the JTc interval may be used in place of the QTc with sponsor approval. Subjects with left bundle branch block are excluded. Subjects with QTc prolongation due to a pacemaker may enroll if the JT is normal or with medical monitor approval.
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: A Phase IB/II Study of Epacadostat (INCB024360) in Combination With Pembrolizumab (MK-3475) and Azacitidine in Subjects With Chemo-refractory Metastatic Colorectal Cancer
Trial Design This is an open label, single-arm, phase IB/II trial to evaluate the safety, tolerability and anti-tumor efficacy of epacadostat (INCB024360) in combination with pembrolizumab (MK-3475) plus azacitidine in patients with chemo-refractory MSS mCRC.
The phase 1B portion of the study will evaluate the safety, tolerability and RP2D of epacadostat (INCB024360) in combination with pembrolizumab plus azacitidine in subjects with chemo-refractory MSS mCRC without any further standard treatment options.
Read more
The phase 2 portion of the study will evaluate the efficacy and safety of epacadostat (INCB024360) in combination with pembrolizumab plus azacitidine in subjects with chemo-refractory MSS mCRC without any further standard treatment options.
In both phase IB and phase 2 portions, patients will receive the combination of azacitidine, pembrolizumab and epacadostat (INCB024360) for the first 18 cycles (Cycles 1-18). Beginning with Cycle 19 through Cycle 35, patients will receive the combination of pembrolizumab and epacadostat (INCB024360).
Read the detailed description
Phase lB Portion:
- The phase 1 portion of this study will be a standard "3+3" design.
- Pembrolizumab will be administered at 200 mg intravenously (IV) on day 1 of each cycle, every 21 days.
- Azacitidine will be administered at 100 mg subcutaneous injection (SQ) daily on days 1-5 of each cycle, every 21 days
- Three dose levels of epacadostat (INCB024360) will be explored: dose levels -1, 1 and 2.
- The dose level 1 will be the starting dose level.
- If the dose level 2 is tolerable without dose limiting toxicities (DLTs), the dose level 2 will be considered the RP2D, and the phase II part will be initiated.
- DLT will be monitored during the first 21 days (cycles 1) and will be used for purposes of dose escalation and determination of RP2D.
- Definition of DLT:
Hematologic Toxicities:
- Any Grade 4 thrombocytopenia or neutropenia lasting > 7 days
- Any Grade 3 thrombocytopenia with severe bleeding
Nonhematologic Toxicities:
- Any Grade 4 toxicity EXCLUDING: Grade 4 abnormal laboratory values with a clear alternative explanation or transient (≤ 72 hours), or without associated clinically significant signs or symptoms based on investigator determination.
- Any Grade 3 or 4 AST, ALT, or total bilirubin elevation
- Any other Grade 3 toxicity EXCLUDING:
- Nausea/vomiting controlled by medical intervention within 72 hours
- Grade 3 rash in the absence of desquamation, no mucosal involvement, does not require systemic steroids, and resolves to Grade 1 within 14 days.
- Grade 3 abnormal laboratory values with a clear alternative explanation or transient (≤ 72 hours), or without associated clinically significant signs or symptoms based on investigator determination.
Phase ll portion:
The phase 2 portion of this study is a non-randomized, open-label, single-arm phase II study. The primary objective of this study is to evaluate objective response rate (ORR) using RECIST1.1.
Study Procedure
- One cycle of therapy is defined as 21 days.
- Subjects may continue treatment up to 35 cycles of the study therapy (the combination of azacitidine, pembrolizumab and epacadostat [INCB024360] for the first 18 cycles [Cycle 1 to Cycle 18], and the combination of pembrolizumab and epacadostat (INCB024360) for the remaining 17 cycles [Cycle 19 to Cycle 35]) until evidence of progression of disease (PD) or unacceptable toxicity.
- Dose-limiting toxicity (DLT) will be assessed during the first 21 days (cycle 1).
- Tumor response will be determined by radiologic measurements by CT and by using RECIST. Assessment of tumor response will be performed every 3 cycles (approximately 9 weeks).
- All patients will be evaluated and graded for adverse events according to the NCI Common Terminology for Adverse Events, version 4.0 (NCI-CTCAE).
Study Treatment
- Pembrolizumab 200 mg will be administered intravenously over 30 minutes on days 1 of each cycle every 21 days.
- Azacitidine 100 mg will be administered as subcutaneous injection on days 1-5 of each cycle every 21 days.
- Epacadostat (INCB024360) will be administered orally twice a day continuously on days 1-21 of each cycle every 21 days. Two dose levels of epacadostat (INCB024360) will be explored: 100 mg BID and 300 mg BID.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Epacadostat (INCB024360) in Combination with Pembrolizumab (MK-3475) and Azacitidine (VIDAZA)
- Keywords
- chemo-refractory, pembrolizumab, epacadostat, azacitidine, recommended phase 2 dose (RP2D), microsatellite-stable (MSS) Metastatic Colorectal Cancer
- Medical subject headings
- Colorectal Neoplasms, Spinocerebellar Degenerations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epacadostat (INCB024360) in Combination with Pembrolizumab (MK-3475) and Azacitidine (VIDAZA)Drug
Oral Epacadostat (INCB024360) (50, 100, or 300 mg twice per day,on days 1-21 of each cycle, every 21 days) in combination with Pembrolizumab (MK-3475) (200 mg IV on days 1 of each cycle, every 21 days) and Azacitidine (VIDAZA) (100 mg SQ daily on days 1-5 of each cycle, every 21 days)
| Study group | Role | What they receive |
|---|---|---|
| Epacadostat + Pembrolizumab + Azacitidine | Experimental | Oral Epacadostat (INCB024360) (50, 100, or 300 mg twice per day,on days 1-21 of each cycle, every 21 days) in combination with Pembrolizumab (MK-3475) (200 mg IV on days 1 of each cycle, every 21 days) and Azacitidine (VIDAZA) (100 mg SQ daily on days 1-5 of each cycle, every 21 days) Receives: Drug: Epacadostat (INCB024360) in Combination with Pembrolizumab (MK-3475) and Azacitidine (VIDAZA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase lB: Recommended phase 2 dose (RP2D) of epacadostat (INCB024360) plus pembrolizumab plus azacitidine
Recommended phase 2 dose (RP2D) of epacadostat (INCB024360) in combination with pembrolizumab plus azacitidine in subjects with chemo-refractory microsatellite-stable (MSS) mCRC without any further standard treatment options.
Measured: Up to 12 months
Phase ll: Objective Response Rate (ORR)
The proportion of patients with the best response of complete response (CR), or partial response (PR) by RECIST1.1 criteria.
Measured: Up to 18 months
Secondary outcomes (3)
Progression-free survival (PFS)
The number of months from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression).
Measured: Up to 18 months
Duration of response (DoR)
The number of months from the date of first response (complete response (CR) or partial response (PR)) until the date of first documented disease progression or death.
Measured: Up to 18 months
Overall survival (OS)
The number of months from the initial date of treatment to the recorded date of death.
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2017
- Study start30 Sep 2018 (estimated)
- Primary completion30 Jul 2019 (estimated)
- Study completion30 Jul 2020 (estimated)
Why it stopped: Study will not be conducted due to changes related to the investigational agent.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- James J Lee
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation, Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, James J Lee, University of Pittsburgh
- Investigators
- James J Lee, MD, PhD, Study chair, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03182894
- Sponsor's protocol ID
- UPCI 16-123
- Status last verified
- Aug 2018
- First submitted
- 7 Jun 2017
- Last updated
- 28 Aug 2018
- Results posted
- No
- 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 28 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IB/II Study of Epacadostat (INCB024360) in Combination With Pembrolizumab (MK-3475) and Azacitidine in Subjects With Chemo-refractory Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03182894
- Acronym / sponsor ID
- UPCI 16-123
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- chemo-refractory, pembrolizumab, epacadostat, azacitidine, recommended phase 2 dose (RP2D), microsatellite-stable (MSS) Metastatic Colorectal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study will not be conducted due to changes related to the investigational agent.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- James J LeeUniversity, hospital or other
- Collaborators
- Incyte Corporation, Merck Sharp & Dohme LLC
- Study start
- 30 Sep 2018 (estimated)
- Primary completion
- 30 Jul 2019 (estimated)
- Study completion
- 30 Jul 2020 (estimated)
- First posted
- 9 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Trial Design This is an open label, single-arm, phase IB/II trial to evaluate the safety, tolerability and anti-tumor efficacy of epacadostat (INCB024360) in combination with pembrolizumab (MK-3475) plus azacitidine in patients with chemo-refractory MSS mCRC.
The phase 1B portion of the study will evaluate the safety, tolerability and RP2D of epacadostat (INCB024360) in combination with pembrolizumab plus azacitidine in subjects with chemo-refractory MSS mCRC without any further standard treatment options.
The phase 2 portion of the study will evaluate the efficacy and safety of epacadostat (INCB024360) in combination with pembrolizumab plus azacitidine in subjects with chemo-refractory MSS mCRC without any further standard treatment options.
In both phase IB and phase 2 portions, patients will receive the combination of azacitidine, pembrolizumab and epacadostat (INCB024360) for the first 18 cycles (Cycles 1-18). Beginning with Cycle 19 through Cycle 35, patients will receive the combination of pembrolizumab and epacadostat (INCB024360).
Detailed description
Phase lB Portion:
- The phase 1 portion of this study will be a standard "3+3" design.
- Pembrolizumab will be administered at 200 mg intravenously (IV) on day 1 of each cycle, every 21 days.
- Azacitidine will be administered at 100 mg subcutaneous injection (SQ) daily on days 1-5 of each cycle, every 21 days
- Three dose levels of epacadostat (INCB024360) will be explored: dose levels -1, 1 and 2.
- The dose level 1 will be the starting dose level.
- If the dose level 2 is tolerable without dose limiting toxicities (DLTs), the dose level 2 will be considered the RP2D, and the phase II part will be initiated.
- DLT will be monitored during the first 21 days (cycles 1) and will be used for purposes of dose escalation and determination of RP2D.
- Definition of DLT:
Hematologic Toxicities:
- Any Grade 4 thrombocytopenia or neutropenia lasting > 7 days
- Any Grade 3 thrombocytopenia with severe bleeding
Nonhematologic Toxicities:
- Any Grade 4 toxicity EXCLUDING: Grade 4 abnormal laboratory values with a clear alternative explanation or transient (≤ 72 hours), or without associated clinically significant signs or symptoms based on investigator determination.
- Any Grade 3 or 4 AST, ALT, or total bilirubin elevation
- Any other Grade 3 toxicity EXCLUDING:
- Nausea/vomiting controlled by medical intervention within 72 hours
- Grade 3 rash in the absence of desquamation, no mucosal involvement, does not require systemic steroids, and resolves to Grade 1 within 14 days.
- Grade 3 abnormal laboratory values with a clear alternative explanation or transient (≤ 72 hours), or without associated clinically significant signs or symptoms based on investigator determination.
Phase ll portion:
The phase 2 portion of this study is a non-randomized, open-label, single-arm phase II study. The primary objective of this study is to evaluate objective response rate (ORR) using RECIST1.1.
Study Procedure
- One cycle of therapy is defined as 21 days.
- Subjects may continue treatment up to 35 cycles of the study therapy (the combination of azacitidine, pembrolizumab and epacadostat [INCB024360] for the first 18 cycles [Cycle 1 to Cycle 18], and the combination of pembrolizumab and epacadostat (INCB024360) for the remaining 17 cycles [Cycle 19 to Cycle 35]) until evidence of progression of disease (PD) or unacceptable toxicity.
- Dose-limiting toxicity (DLT) will be assessed during the first 21 days (cycle 1).
- Tumor response will be determined by radiologic measurements by CT and by using RECIST. Assessment of tumor response will be performed every 3 cycles (approximately 9 weeks).
- All patients will be evaluated and graded for adverse events according to the NCI Common Terminology for Adverse Events, version 4.0 (NCI-CTCAE).
Study Treatment
- Pembrolizumab 200 mg will be administered intravenously over 30 minutes on days 1 of each cycle every 21 days.
- Azacitidine 100 mg will be administered as subcutaneous injection on days 1-5 of each cycle every 21 days.
- Epacadostat (INCB024360) will be administered orally twice a day continuously on days 1-21 of each cycle every 21 days. Two dose levels of epacadostat (INCB024360) will be explored: 100 mg BID and 300 mg BID.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Epacadostat + Pembrolizumab + Azacitidine | Experimental | Drug: Epacadostat (INCB024360) in Combination with Pembrolizumab (MK-3475) and Azacitidine (VIDAZA)Oral Epacadostat (INCB024360) (50, 100, or 300 mg twice per day,on days 1-21 of each cycle, every 21 days) in combination with Pembrolizumab (MK-3475) (200 mg IV on days 1 of each cycle, every 21 days) and Azacitidine (VIDAZA) (100 mg SQ daily on days 1-5 of each cycle, every 21 days) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
- The diagnosis of microsatellite-stable (MSS) mCRC will be based on histologic or cytologic confirmation. The histologic or cytologic confirmation of MSS status will be based on CLIA-certified immunohistochemistry (IHC) or PCR assay.
- Have mCRC that has been previously treated with currently approved standard therapies, including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy.
- Have measurable disease based on RECIST1.1.
Key exclusion criteria (31 listed)
- 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 chronic systemic steroid therapy (in doses exceeding 10mg daily of prednisone equivalent) 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 4 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.
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 |
|---|---|---|
| Epacadostat (INCB024360) in Combination with Pembrolizumab (MK-3475) and Azacitidine (VIDAZA)Oral Epacadostat (INCB024360) (50, 100, or 300 mg twice per day,on days 1-21 of each cycle, every 21 days) in combination with Pembrolizumab (MK-3475) (200 mg IV on days 1 of each cycle, every 21 days) and Azacitidine (VIDAZA) (100 mg SQ daily on days 1-5 of each cycle, every 21 days) | Drug | Epacadostat + Pembrolizumab + Azacitidine |
Primary outcome
Phase lB: Recommended phase 2 dose (RP2D) of epacadostat (INCB024360) plus pembrolizumab plus azacitidine
Time frame: Up to 12 months
Recommended phase 2 dose (RP2D) of epacadostat (INCB024360) in combination with pembrolizumab plus azacitidine in subjects with chemo-refractory microsatellite-stable (MSS) mCRC without any further standard treatment options.
Phase ll: Objective Response Rate (ORR)
Time frame: Up to 18 months
The proportion of patients with the best response of complete response (CR), or partial response (PR) by RECIST1.1 criteria.
3 secondary outcomes
Progression-free survival (PFS)
Time frame: Up to 18 months
Duration of response (DoR)
Time frame: Up to 18 months
Overall survival (OS)
Time frame: Up to 18 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2018.
- 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.
James J Lee, MD, PhD study chair
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Epacadostat (INCB024360) in Combination with Pembrolizumab (MK-3475) and Azacitidine (VIDAZA) in people with Metastatic Colorectal Cancer, run by James J Lee 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 31 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: withdrawn, as of the sponsor's last update on 28 Aug 2018. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Phase lB: Recommended phase 2 dose (RP2D) of epacadostat (INCB024360) plus pembrolizumab plus azacitidine (time frame: Up to 12 months). The study lists 2 primary outcomes in all. 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 28 Aug 2018.