Clinical Trials /

Durvalumab Before Surgery in Treating Patients With Oral Cavity or Oropharynx Cancer

NCT02827838

Description:

This pilot clinical trial studies how well durvalumab before surgery works in treating patients with oral cavity or oropharynx cancer. Monoclonal antibodies, such as durvalumab, may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab Before Surgery in Treating Patients With Oral Cavity or Oropharynx Cancer
  • Official Title: Pilot Study to Evaluate the Anti-Tumor Effect of Durvalumab (Medi4736) in Patients With Squamous Cell Carcinoma of the Head and Neck (SCCHN), Human Papilloma Virus (HPV) Positive Versus Negative, When Treated Before Surgery

Clinical Trial IDs

  • ORG STUDY ID: IRB00038877
  • SECONDARY ID: NCI-2016-00639
  • SECONDARY ID: CCCWFU 60116
  • SECONDARY ID: P30CA012197
  • NCT ID: NCT02827838

Conditions

  • Human Papillomavirus Infection
  • Stage I Oral Cavity Squamous Cell Carcinoma
  • Stage I Oropharyngeal Squamous Cell Carcinoma
  • Stage II Oral Cavity Squamous Cell Carcinoma
  • Stage II Oropharyngeal Squamous Cell Carcinoma
  • Stage III Oral Cavity Squamous Cell Carcinoma
  • Stage III Oropharyngeal Squamous Cell Carcinoma
  • Stage IVA Oral Cavity Squamous Cell Carcinoma
  • Stage IVA Oropharyngeal Squamous Cell Carcinoma
  • Stage IVB Oral Cavity Squamous Cell Carcinoma
  • Stage IVB Oropharyngeal Squamous Cell Carcinoma
  • Stage IVC Oropharyngeal Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
DurvalumabImmunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736Treatment (durvalumab, surgery)

Purpose

This pilot clinical trial studies how well durvalumab before surgery works in treating patients with oral cavity or oropharynx cancer. Monoclonal antibodies, such as durvalumab, may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To investigate the effect of durvalumab on local and systemic immune activation by HPV
      status in patients with oral cavity and oropharynx head and neck squamous cell carcinoma
      (HNSCC).

      II. To examine the effects of durvalumab on systemic immune response to HPV and tumor
      associated antigens.

      III. To examine the effects of durvalumab on immune regulatory mechanisms. IV. To explore the
      association between levels of immune-regulatory micro-ribonucleic acid (miR) in plasma and
      saliva and immune response.

      SECONDARY OBJECTIVES:

      I. Investigate the effect of the treatment with durvalumab on the computed tomography (CT)
      scan and positron emission tomography (PET) scan response.

      II. Evaluate the safety of a short induction treatment with durvalumab.

      OUTLINE:

      Patients receive durvalumab intravenously (IV) over approximately 60 minutes on day 1.
      Treatment repeats every 2 weeks for up to 2 courses in the absence of disease progression or
      unacceptable toxicity. Within 3-17 days after last dose administration of durvalumab,
      patients undergo surgery. Patients may receive an additional dose of durvalumab if time to
      surgery is longer than 30 days.

      After completion of study treatment, patients are followed up for 90 days.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (durvalumab, surgery)ExperimentalPatients receive durvalumab IV over approximately 60 minutes on day 1. Treatment repeats every 2 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Within 3-17 days after last dose administration of durvalumab, patients undergo surgery. Patients may receive an additional dose of durvalumab if time to surgery is longer than 30 days.
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed HNSCC of the oral cavity (OC; more than 90%
             patients have HPV negative cancer) or oropharynx (about 60-80% of patient have HPV
             positive cancer)

          -  Presence of radiologically documented disease; all radiology studies must be performed
             within 28 days prior to registration

          -  Any stage, considered candidates for surgery and scheduled for surgery either by
             robotic or by standard surgical technique

          -  Documentation of HPV tested by polymerase chain reaction (PCR)

          -  Willing to provide consent for an additional tissue biopsy for research purposes, to
             allow a part of their surgical tumor tissue to be utilized for research (in case tumor
             tissue has not already been saved in the tumor tissue bank), and to donate samples of
             blood and saliva collected weekly through the treatment

          -  All patients must have provided informed consent for correlative studies

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Patients must have no prior exposure to immune-mediated therapy, including anti-
             cytotoxic T-lymphocyte protein 4 (CTLA-4), anti-programmed cell death 1 (PD-1),
             anti-programmed cell death 1 ligand 1 (PD-L1), or anti-programmed cell death ligand 2
             antibodies, excluding therapeutic anticancer vaccines

          -  At least 1 lesion, not previously irradiated, that can be accurately measured at
             baseline as >= 10 mm in the longest diameter (except lymph nodes, which must have a
             short axis >= 15 mm) with CT or magnetic resonance imaging (MRI) and that is suitable
             for accurate repeated measurements as per Response Evaluation Criteria in Solid Tumors
             (RECIST) 1.1 guidelines

          -  Previous surgery is permitted provided that a minimum of 28 days (4 weeks) have
             elapsed between any major surgery and date of registration, and that wound healing has
             occurred

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

          -  Platelet count >= 100 x 10^9/L

          -  Hemoglobin >= 9.0 g/dL

          -  Serum bilirubin =< 1.5 x upper limit of normal (ULN) (institutional upper limit of
             normal)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

          -  Serum creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula or by
             24-hour urine collection for determination of creatinine clearance

          -  Female subjects must either be of non-reproductive potential (ie, post-menopausal by
             history: >= 60 years old and no menses for >= 1 year without an alternative medical
             cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history
             of bilateral oophorectomy) or must have a negative serum pregnancy test upon study
             entry

          -  In accordance with National Cancer Institute of Canada Clinical Trials Group (NCIC
             CTG) policy, protocol treatment is to begin within 2 working days of patient
             registration

          -  Written informed consent and any locally-required authorization (e.g., Health
             Insurance Portability and Accountability Act [HIPAA] in the United States of American
             [USA], European Union [EU] Data Privacy Directive in the EU) obtained from the subject
             prior to performing any protocol-related procedures, including screening evaluations

          -  Subject is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up

        Exclusion Criteria:

          -  Participation in another clinical study with an investigational product during the
             last 6 months (mo)

          -  Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab

          -  Receipt of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy,
             targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other
             investigational agent) within the last 6 mo

          -  Mean QT interval corrected for heart rate (corrected QT [QTc]) >= 470 ms calculated
             from 3 electrocardiograms (ECGs) using Fridericia's correction

          -  Current or prior use of immunosuppressive medication within 28 days before the first
             dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or
             systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
             prednisone, or an equivalent corticosteroid

          -  Any unresolved toxicity (> Common Terminology Criteria for Adverse Events [CTCAE]
             grade 2) from previous anti-cancer therapy; subjects with irreversible toxicity that
             is not reasonably expected to be exacerbated by the investigational product may be
             included (e.g., hearing loss, peripherally neuropathy)

          -  Any prior grade >= 3 immune-related adverse event (irAE) while receiving any previous
             immunotherapy agent, or any unresolved irAE > grade 1

          -  Active or prior documented autoimmune disease within the past 2 years; NOTE: Subjects
             with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
             the past 2 years) are not excluded

          -  Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
             ulcerative colitis)

          -  History of primary immunodeficiency

          -  History of allogeneic organ transplant

          -  History of hypersensitivity to durvalumab or any excipient

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
             bleeding diatheses including any subject known to have evidence of acute or chronic
             hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
             illness/social situations that would limit compliance with study requirements or
             compromise the ability of the subject to give written informed consent

          -  Known history of active tuberculosis

          -  Receipt of live attenuated vaccination within 30 days prior to study entry or within
             30 days of receiving durvalumab

          -  Female subjects who are pregnant, breast-feeding or male or female patients of
             reproductive potential who are not employing an effective method of birth control

          -  Patients with body weight <= 30 kg

          -  Any condition that, in the opinion of the investigator, would interfere with
             evaluation of study treatment or interpretation of patient safety or study results
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Immune effector assessed in blood by flow cytometry and in tissue by immunohistochemistry
Time Frame:Up to 18 months
Safety Issue:
Description:Concentration of certain immune effector will be assessed in blood pre- and post- treatment. Descriptive statistics, confidence intervals will be calculated and 2-sample t-tests will be performed. Tumor-infiltrating immune-regulator and effector cells will be quantified (0 to 3+) using standing immunofluorescence techniques. Counts and percents will be calculated for these measures overall and by HPV (+/-) groups pre- and post-treatment. Fisher exact tests will be used to compare groups at pre- and post- treatment. Stuart-Maxwell tests (generalizations of the McNemar's Tes

Secondary Outcome Measures

Measure:Incidence of adverse events (AEs) as measured by CTCAE version 4.03
Time Frame:Up to 90 days
Safety Issue:
Description:AEs will be coded using the Medical Dictionary for Regulatory Activities to their organ class by preferred term. Coded AEs will be displayed by frequency, severity, and relationship to treatment (durvalumab) in the safety population. In addition, summary tables will be generated for the following situations: 1. fatigue, diarrhea, nausea and skin rash; 2. Immune-mediated reactions of any grade; 3. other adverse events graded as 3 or more by CTCAE Version 4.03; 4) Durvalumab dose reductions; 5) discontinuations of treatment with durvalumab, with specification of reason for discontinuation; and 6
Measure:Standardized Uptake Value (SUV) as measured by PET scans
Time Frame:Up to 18 months
Safety Issue:
Description:SUV activity as measured by PET scans will also be compared between groups at each time point and descriptive statistics, confidence intervals will be calculated and 2-sample t-tests will be performed.
Measure:Tumor volume assessed using RECIST version 1.1 criteria
Time Frame:Up to 18 months
Safety Issue:
Description:Tumor volumes will be compared between groups (HPV +/-) pre- and post- treatment. Descriptive statistics, confidence intervals will be calculated and 2-sample t-tests will be performed

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Wake Forest University Health Sciences

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