A Study of Epacadostat + Pembrolizumab in Head and Neck Cancer Patients, Who Failed Prior PD-1/PD-L1 Therapy

NCT03238638 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: IRB15-1631
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study to test the combination of two drugs, pembrolizumab and epacadostat with the goal of benefiting subjects with head and neck cancers where prior or ongoing regimens with a PD-1 or PD-L1 inhibitor for the treatment of advanced head and neck cancer after platinum failure.

Conditions

Head and Neck Cancer

Keywords

Epacadostat; Pembrolizumab; PD-1; PD-L1

Outcome Measures

Primary Outcomes (1)

• Patient response rate

  The number of patients with responses per RECIST 1.1 will be compared to the total number of patients in each cohort (which is anticipated to enroll 15).

  From the start of treatment to the time of response until disease progression, death, or end of trial, whichever comes first, not to exceed 5 years.

Secondary Outcomes (3)

• Overall survival rate

  From the time of enrollment until death, withdrawal of consent, or the end of the study, whichever occurs first OR at most 2 years out from the last patient receiving treatment.

• One year progression free rate

  From the time of enrollment until the first documented disease progression, death, withdrawal of consent, or the end of the study, whichever occurs first OR at most 2 years out from the last patient receiving treatment.

• Number of patients with adverse events

  From the start of treatment until the end of study, not to exceed 5 years.

Study Arms (1)

Acquired Resistance Cohort and Suboptimal Benefit Cohort

EXPERIMENTAL

Patients will be divided into two cohorts. Investigators anticipate 15 patients per cohort. Cohort 1: Acquired Resistance Cohort * Treat upon emergence of acquire resistance * Prior benefit from an9-PD-1/PD-L1 therapy defined as a. preior response, and/or b. greater than or equal to 5 months of stable disease * Progressive disease on recent scans * Intercurrent therapy is allowed Cohort 2: Suboptimal Benefit Cohort * Treat subop. mal response/benefit, BEFORE emergence of acquired resistance * Prolonged stable disease greater than or equal to 5 months OR Subop9mal response (greater than 10% and less than 50%) * Ongoing stable disease on recent scans Both cohorts will receive pembrolizumab and epacadostat.

Drug: Pembrolizumab; Drug: epacadostat

Interventions

Pembrolizumab DRUG

Both cohorts will receive pembrolizumab at a flat dose of 200mg every 3 weeks.

Also known as: Keytruda

Acquired Resistance Cohort and Suboptimal Benefit Cohort

epacadostat DRUG

Both cohorts will receive epacadostat. Patients in cohort 1 will take 300mg of epacadostat by mouth twice per day. Cohort 2 will take 300mg of epacadostat every 6 weeks.

Acquired Resistance Cohort and Suboptimal Benefit Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patients must have histologically confirmed squamous cell carcinoma of the head and neck (unresectable and not amenable to curative intent therapy)
• \. Meet criteria for either the Acquired Resistance OR the Suboptimal Benefit Cohort
• a. Acquired Resistance is 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.
• ii. Progressive Disease (PD) on recent scans b. 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
• \. 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 per RECIST 1.1.
• \. Known HPV status
• \. ECOG performance status 0 or 1
• \. Be willing and able to provide written informed consent/assent for the trial.
• \. Be greater than or equal to 18 years of age on day of signing informed consent.
• \. Demonstrate reasonable organ function as defined below, all screening labs should be performed within 10 days of treatment initiation.
• System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) Renal Serum creatinine OR Measured or calculateda creatinine clearance ≤1.5 X upper limit of normal (ULN) OR (GFR can also be used in place of creatinine or CrCl) ≥40 mL/min for subject with creatinine levels \> 2.0 X institutional ULN Hepatic Serum total bilirubin ≤ 1.2 X ULN OR in case of Gilbert's disease an elevated total Bilirubin is allowed if direct Bilirubin is ≤40% of total AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN
• Coagulation International Normalized Ratio (INR) or Prothrombin Time ≤1.5 X ULN unless subject is receiving (PT) anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• \*Creatinine clearance should be calculated per institutional standard.

You may not qualify if:

• \. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 2 weeks of the first dose of treatment.
• \. Has a 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.
• \. Has a known history of active TB (Bacillus Tuberculosis)
• \. Has hypersensitivity to pembrolizumab, epacadostat or any of its excipients.
• \. Has had a 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).
• Note: Subjects 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-coargulants (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.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

pembrolizumab; epacadostat

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2017
• First Posted: August 3, 2017
• Study Start: September 1, 2018
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: January 4, 2018

Record last verified: 2018-01

Locations

US (1)