Epacadostat (INCB024360) Added to Preoperative Chemoradiation in Patients With Locally Advanced Rectal Cancer
Phase I/II Study of Epacadostat (INCB024360) Added to Preoperative Chemoradiation in Patients With Locally Advanced Rectal Cancer
2 other identifiers
interventional
49
1 country
4
Brief Summary
The purpose of this research study is to evaluate epacadostat when given with routine radiation therapy and chemotherapy (capecitabine and oxaliplatin) to treat rectal cancer before routine surgery is performed to remove the tumor.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jan 2020
Longer than P75 for phase_1
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 24, 2018
CompletedFirst Posted
Study publicly available on registry
May 4, 2018
CompletedStudy Start
First participant enrolled
January 6, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 15, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 12, 2030
February 11, 2026
February 1, 2026
7.5 years
April 24, 2018
February 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Phase I only: Recommended phase II dose (RP2D) of epacadostat with standard of care radiation and chemotherapy in preoperative treatment of locally advanced rectal cancer
The recommended phase 2 dose (RP2D) is defined as the dose level immediately below the maximally administered dose at which 0 or 1 of a cohort of 3 to 6 patients experienced a dose-limiting toxicity (DLT) during first 2 cycles.
Completion of the first 2 cycles of treatment for all patients (estimated to be 86 months)
Phase II Treatment Cohort only: Neoadjuvant Rectal (NAR) Score
Neoadjuvant Rectal Score (NAR Score) is calculated by following formula: NAR = (\[5pN \- 3(cT - pT) + 12\]2)/9.61 (with higher scores representing poorer prognosis), where cT=clinical tumor stage, pT=pathologic tumor stage, and pN=pathologic nodal stage.
At the time of surgery (approximately week 28)
Secondary Outcomes (5)
Phase I and Phase II Treatment Cohort only: Safety and toxicity profile of the combination as measured by adverse events experienced
Through 4 weeks after completion of treatment (approximately 28 weeks)
Phase I only: Neoadjuvant Rectal (NAR) Score
At the time of surgery (approximately week 28)
Phase I and Phase II Treatment Cohort only: Pathological complete response rate (pCR)
At the time of surgery (approximately week 25)
Phase I and Phase II Treatment Cohort only: Progression-free survival (PFS)
Through completion of follow-up (estimated to be 3 years and 32 weeks)
Phase I and Phase II Treatment Cohort only: Complete clinical response rate (cCR)
At the time of preoperative assessment (approximately week 28)
Study Arms (3)
Dose Escalation Cohort (Phase I): Epacadostat + SCRT + Chemotherapy + Surgery
EXPERIMENTAL* Epacadostat at the designated dose level starting on the 1st day of radiation therapy and continuing throughout chemotherapy until the day of surgery. * Standard of care preoperative therapy will consist of a total of approximately 20-24 weeks of short-course pelvic radiation and chemotherapy: * Cycle 0 Days 1-7(Week 1): Short-course pelvic radiation therapy (SCRT), 5 fractions over 1 week * Cycle 0 Days 8-21 or 8-28 (Weeks 2-4): Treatment break for 2 to 3 weeks; for patients enrolled at Washington University and Dana Farber only, tumor biopsy will be obtained between the end of RT and prior to chemotherapy (target Days 14-28) * Cycles 1-6: (6) 21-day cycles of CAPOX for a total of 18 weeks. CAPOX is typically capecitabine at 1000 mg/m\^2 PO BID (days 1-14 of each cycle) and oxaliplatin 130 mg/m\^2 IV Q3W. * Surgery will follow approximately 4 to 6 weeks after completion of CAPOX
Phase II Treatment Cohort: Epacadostat + SCRT + Chemotherapy + Surgery
EXPERIMENTAL* Epacadostat 400 mg BID 1st day of radiation therapy and continuing for \~28 days, until biopsy (with the exception of patients enrolling to dose expansion and starting on epacadostat with neoadjuvant chemotherapy prior to approval of post-sIRB A2) * Preoperative therapy approximately 20-24 weeks of chemoradiation: * Week 1: SCRT, typically 5 Gy x 5 fractions over 1 week, with epacadostat 400 mg BID starting on D1 of SCRT * Weeks 2-4: Epacadostat monotherapy 400 mg BID \& continued for a minimum of 21 days, until the day prior to chemotherapy * For patients enrolled at Washington University and Dana Farber Cancer Institute ONLY, tumor biopsy between the end of RT and prior to initiation of chemotherapy. Tumor biopsy target of between Days 15-28 * Weeks 3-6: 4-5 weeks after completion of SCRT \& after completion of approximately 21-35 days of epacadostat, SOC neoadjuvant chemotherapy of CAPOX or FOLFOX will be initiated * Surgery will occur approximately 4-6 weeks after chemotherapy
Phase II Biomarker Cohort: SCRT + Chemotherapy + Surgery
ACTIVE COMPARATORWashington University and Dana Farber only: Patients enrolled to this cohort will not receive epacadostat. Patients will undergo standard of care preoperative therapy consisting of approximately 20 to 24 weeks of chemoradiation. All treatment will be administered in this cohort as per institutional standard. The expected schedule for these patients will consist of 1 week of short-course pelvic radiation therapy, followed by a treatment break, followed by neoadjuvant chemotherapy. Approximately 4 to 6 weeks after completion of neoadjuvant chemotherapy, patients may undergo surgery. Tumor biopsy may occur at screening and after completion of RT, prior to starting neoadjuvant chemotherapy.
Interventions
Drug provided.
Short-course pelvic radiation therapy, 5 Gy x 5 fractions over 1 week
Standard of care
Standard of care
Eligibility Criteria
You may qualify if:
- Newly diagnosed pathologically-confirmed locally advanced rectal cancer (defined by 8th edition AJCC stage 2 or 3, or stage 1 not eligible for sphincter-sparing surgery) with plans to proceed with total neoadjuvant short course radiation as part of their neoadjuvant therapy as confirmed by treating physician
- At least 18 years of age.
- ECOG performance status 0, 1, or 2
- Adequate bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1.5 K/cumm
- Platelets ≥ 100 K/cumm
- Hemoglobin \> 9 g/dL
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
- Serum creatinine \< 1.5 x IULN OR measured or calculated creatinine clearance ≥ 50 mL/min/1.73 m2
- Applicable to subjects enrolled at Washington University and Dana Farber Cancer Institute only: Willing to undergo study-related biopsies subject to accessibility of tumor, appropriateness of biopsy (not contraindicated), and continued subject consent. If biopsy is not safe and feasible per treating physician, then patient may still enroll with permission of sponsor-investigator.
- Women of childbearing potential and men must agree to contraceptive methods as described in protocol prior to study entry, for the duration of study participation, and for 120 days after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
You may not qualify if:
- Received prior anti-cancer therapy for rectal cancer.
- Prior treatment with agents targeting IDO pathway (including indoximod)
- Previous radiotherapy in the pelvic region or previous rectal surgery (e.g. TEM) or any investigational treatment for rectal cancer within the past month.
- Known or suspected presence of another malignancy that could be mistaken for the malignancy under study during disease assessments.
- Currently receiving any other investigational agents.
- Extensive growth into cranial part of the sacrum (above S3) or the lumbosacral nerve roots indicating that surgery will never be possible even if substantial tumor downsizing is seen.
- Presence of metastatic disease or recurrent rectal tumor.
- Diagnosis of Familial Adenomatosis Polyposis coli (FAP), Hereditary Non-Polyposis Colorectal Cancer (HNPCC), active Crohn's disease, or active ulcerative colitis.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to epacadostat, pembrolizumab, 5-FU, oxaliplatin, or other agents used in the study.
- Has an active infection requiring systemic therapy.
- Warfarin (Coumadin): patients currently on warfarin are excluded. Patients who go off warfarin and have INR within normal limits have no washout period.
- Any history of serotonin syndrome (SS) after receiving serotonergic drugs. This syndrome has been most closely associated with the use of MAOIs, meriperidine, linezolid, or methylene blue; all of these agents are prohibited during the study
- Uncontrolled intercurrent illness including, but not limited to active tuberculosis infection, pneumonitis requiring treatment, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
- Has an active or inactive autoimmune disease or syndrome (i.e. rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease) that has required systemic treatment in the past 2 years or is receiving systemic therapy for an autoimmune or inflammatory disease (i.e. with use of modifying agents, corticosteroids, or immunosuppressive drugs). Exceptions include subjects with vitiligo or resolved childhood asthma/atopy, hypothyroidism stable on hormone replacement, controlled asthma, Type I diabetes, Graves' disease, or Hashimoto's disease.
- An abnormal screening ECG that, in the investigator's opinion, is clinically meaningful.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Washington University School of Medicinelead
- Incyte Corporationcollaborator
- National Cancer Institute (NCI)collaborator
Study Sites (4)
University of California Irvine - Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Henry Ford Cancer Institute
Detroit, Michigan, 48202, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Moh'd Khusman, M.D.
Washington University School of Medicine
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 24, 2018
First Posted
May 4, 2018
Study Start
January 6, 2020
Primary Completion (Estimated)
July 15, 2027
Study Completion (Estimated)
August 12, 2030
Last Updated
February 11, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will not share