Ignite Creation Date:
2025-12-25 @ 1:32 AM
Ignite Modification Date:
2025-12-26 @ 2:27 AM
Study NCT ID:
NCT03182894
Status:
WITHDRAWN
Last Update Posted:
2018-08-28
First Post:
2017-06-07
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Epacadostat in Combination With Pembrolizumab and Azacitidine in Subjects With Metastatic Colorectal Cancer
Sponsor:
James J Lee
Organization:
Study Overview
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
Status:
WITHDRAWN
Status Verified Date:
2018-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Study will not be conducted due to changes related to the investigational agent.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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).
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:
o 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.
* 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:
o 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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: