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Neoadjuvant Pembrolizumab + Epacadostat Prior to Curative Surgical Care for Squamous Cell Carcinoma of the Head and Neck

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ClinicalTrials.gov Identifier: NCT03325465
Recruitment Status : Withdrawn (Site decided not to move forward with trial. Study never opened to enrollment.)
First Posted : October 30, 2017
Last Update Posted : April 22, 2019
Sponsor:
Information provided by (Responsible Party):
University of Chicago

Brief Summary:

The KEO study is a single arm phase II trial including 44 patients with T1N1-2B, T2N0-N2B head and neck squamous cell carcinoma (HNSCC) eligible for curative-intent resection (+/- adjuvant therapy), who receive neo-adjvuant pembrolizumab + epacadostat.

The primary objective of this study is to determine rate of major treatment effect (MTE) to neoadjuvant pembrolizumab+epacostat immunotherapy in SCCHN compared to historic data with neoadjuvant pembrolizumab alone.


Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of the Head and Neck Drug: Pembrolizumab Drug: Epacadostat Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Pembrolizumab + Epacadostat Prior to Curative Surgical Care for Squamous Cell Carcinoma of the Head and Neck (SCCHN): The KEO Trial
Actual Study Start Date : January 22, 2018
Actual Primary Completion Date : November 7, 2018
Actual Study Completion Date : November 7, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pembrolizumab and epacadostat

Patients will receive neoadjuvant immunotherapy either with anti-PD-1 (pembrolizumab) alone or anti-PD-1 in combination with IDO1 inhibition (epacadostat). Patients will receive Pembrolizumab every 3 weeks over a period of 8 weeks as well as epacadostat starting on day 1 for the duration of pembrolizumab treatment.

All patients will undergo baseline biopsy (mandatory, sampling ≥ 4 areas to represent the tumor), as well as baseline imaging (and for exploratory analysis collection of blood for baseline ctDNA testing and TCR analysis).

Drug: Pembrolizumab
Patients will receive pembrolizumab alone or pembrolizumab in combination with epacadostat. Pembrolizumab will be administered at 200 mg IV every 3 weeks for up to 3 doses for no longer than 8 weeks prior to surgery. After surgery, patients will continue pembrolizumab plus epacadostat every 3 weeks for 12 months.
Other Name: Keytruda

Drug: Epacadostat
Patients will receive epacadostat in combination with pembrolizumab. Epacadostat will be administered orally at a dose of 100 mg twice a day starting on day 1 for the duration of pembrolizumab treatment. Patients will continue on this combination for no longer than 8 weeks prior to surgery. After surgery, patients will continue pembrolizumab plus epacadostat every 3 weeks for 12 months.




Primary Outcome Measures :
  1. Rate of major treatment effect (rate of treatment response) [ Time Frame: 3-4 weeks after patient has begun treatment ]
    MTE will be assessed in the same way as done by Uppaluri et al (Uppaluri ASCO 2017) upon pathologic review and assessment of 50% resolution of tumor with active immune response (termed "major treatment effect" in their study).

  2. Rate of complete response [ Time Frame: 8 weeks after patient has begun treatment ]
    Response rate at surgery compared to historic data with chemotherapy


Secondary Outcome Measures :
  1. Progression free survival rate [ Time Frame: From the start of treatment to the first documented report of disease progression or death, whichever comes first, not to exceed 100 months. ]
  2. Overall survival rate [ Time Frame: From the start of treatment to the time of death, not to exceed 100 months. ]
  3. Number of patients with adverse events prior to and after surgery [ Time Frame: Up to 2 years ]
  4. Complete response rate [ Time Frame: From the start of treatment to the first documented report of response, disease progression, or death, whichever comes first, not to exceed 100 months. ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be willing and able to provide written informed consent/assent for the trial.
  • Be 18 years of age or older on day of signing informed consent.
  • Patients with non-bulky/non-bulky squamous cell carcinomas of the head and neck, with an indication for surgical therapy.

    1. T1N1-N2B, T2-4N0-N2b stage are generally eligible
    2. If determined per tumor board that a low-volume/non-bulky tumor of another stage is appropriate for resection (e.g. small volume T4 with a small amount of bone invasion) such tumors may also be considered for this study if recommendation in tumor board is such.
  • Be appropriate candidates for resection and curative intent therapy in general.
  • Have a performance status of 0 or 1 on the ECOG Performance Scale.
  • Consent to undergo biopsy from a newly obtained core or excisional biopsy of a tumor lesion before study drug administration, and during treatment. Biopsy in case of progressive disease is optional.
  • Ability to swallow tablets (at future point administration via G-tube may be allowed if approved by drug manufacturer)
  • Measurable disease per RECIST 1.1.
  • Known HPV status for oropharyngeal primary tumors.
  • Pre-operative scans including MRI/CT neck and, CT chest with contrast. If contrast is contraindicated, Staging PET or PET-CT is acceptable although high quality / diagnostic cross-sectional imaging of the head and neck area is recommended.
  • Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.

Table 1 Adequate Organ Function Laboratory Values 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 within upper limit of normal (ULN) OR

Measured or calculateda creatinine clearance ≥60 mL/min for subject with creatinine (GFR can also be used in place of creatinine or levels > institutional ULN CrCl)

Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN

AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN

Albumin >2.5 mg/dL

Coagulation International Normalized Ratio (INR) or ≤1.5 X ULN unless subject is receiving Prothrombin Time (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 aCreatinine clearance should be calculated per institutional standard.

  • 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 should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Abstinence is considered an adequate contraception method.

Exclusion Criteria:

  • Has a diagnosis now or in the past of immunodeficiency requiring systemic steroid therapy in excess of physiologic dose (or any other form of immunosuppressive therapy within 10 days prior to the first dose of trial treatment).
  • Has bulky tumor (define as N3 lymph node or equivalent lymph conglomerate (≥ 6 cm in one dimension), or primary tumor > 4 cm). Cystic HPV+ lymph nodes should be assessed in tumor board and may not be considered bulky.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Other life-threatening illness that is expected to impact life expectancy within 3 years.
  • Hypersensitivity to pembrolizumab, epacadostat or any of its excipients.
  • Has a known additional malignancy that was diagnosed within the last five years that is either 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 in a broader sense is not felt to impact life-expectancy.
  • Has active autoimmune disease that has required systemic (large physiologic dose) treatment in the past year (i.e. with use of disease modifying agents, corticosteroids or any other 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 immunosuppressive treatment.
  • History of non-infectious pneumonitis requiring steroids or current pneumonitis
  • Has an active viral 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 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 of planned start of study therapy.
  • Allogeneic organ or stem cell transplant
  • History of interstitial lung disease (ILD)/pneumonitis requiring treatment with steroids and patients with active ILD/pneumonitis

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03325465


Locations
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United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
Investigators
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Principal Investigator: Tanguy Seiwert, MD University of Chicago

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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT03325465     History of Changes
Other Study ID Numbers: IRB17-0993
First Posted: October 30, 2017    Key Record Dates
Last Update Posted: April 22, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Chicago:
squamous cell carcinoma of the head and neck
head and neck cancer
neoadjuvant pembrolizumab
epacadostat

Additional relevant MeSH terms:
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Pembrolizumab
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Antineoplastic Agents, Immunological
Antineoplastic Agents