Clinical Trials /

Study of MEDI0562 Prior to Surgical Resection in Head and Neck Squamous Cell Carcinoma (HNSCC) or Melanoma

NCT03336606

Description:

This clinical trial will evaluate the safety and feasibility of a humanized OX40 agonist, MEDI0562, in the pre-operative setting for patients with head and neck squamous cell carcinoma or melanoma.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of MEDI0562 Prior to Surgical Resection in Head and Neck Squamous Cell Carcinoma (HNSCC) or Melanoma
  • Official Title: Phase Ib Study of a Monoclonal Antibody to OX40 (MEDI0562) Administered Prior to Surgical Resection in Patients With Head and Neck Squamous Cell Carcinoma or Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 2017000254 17Aug2017
  • NCT ID: NCT03336606

Conditions

  • Head and Neck Cancer
  • Head and Neck Squamous Cell Carcinoma
  • Melanoma
  • Cell Cancer, Squamous
  • Carcinoma, Squamous Cell

Interventions

DrugSynonymsArms
MEDI0562Surgical ResectionCohort I

Purpose

This clinical trial will evaluate the safety and feasibility of a humanized OX40 agonist, MEDI0562, in the pre-operative setting for patients with head and neck squamous cell carcinoma or melanoma.

Detailed Description

      This clinical trial is the first to evaluate the safety and feasibility of a humanized OX40
      agonist, MEDI0562, in the pre-operative setting for patients with head and neck squamous cell
      carcinoma or melanoma.

      Patients will be randomly assigned to one of two MEDI0562 administration schedules; initially
      5 patients will enroll to each cohort. All patients will have a tumor biopsy before
      administration of MEDI0562 and surgery will be performed on approximately day 15 (+/- 2
      days).

      There will be a comparison of a surgical specimen to the original biopsy focusing on the
      composition and immunologic phenotypes of lymphocyte subsets. Although the primary endpoint
      of this study is immunological, valuable exploratory data on clinical outcomes will also be
      obtained.

      Both the HNSCC and the melanoma patients to be enrolled on this trial are anticipated to have
      a 50 - 90% probability of recurrence within 5 years after surgery, even with current
      state-of-the-art post-surgical adjuvant radiation, chemotherapy, or immunotherapy. A
      recurrence of 25% or less within the 12 months after surgery will be deemed of clinical
      interest and would inform the design of a larger follow-up study.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort IActive ComparatorMEDI0562 administration (90mg on day 1) followed by surgical resection (day 15)
  • MEDI0562
Cohort IIActive ComparatorMEDI0562 administration (30mg on days 1, 3, 5) followed by surgical resection (day 15)
  • MEDI0562

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with advanced head and neck squamous cell carcinoma (HNSCC) or stage
             IIIb/IIIC melanoma who are candidates for R0 surgical resection

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

          -  Age 18 years or above

          -  Laboratory values:

               -  WBC ≥2000/uL

               -  Hgb >8g/dl (patients may be transfused to reach this level)

               -  Platelets >75,000 cells/mm3

               -  Serum creatinine 3 X upper limit of laboratory normal

               -  Negative bHCG (urine/serum) [women of childbearing potential only]

               -  AST (SGOT) and ALT (SGPT) <2.5 X upper limit of laboratory normal

               -  Alkaline phosphatase <2.5 X upper limit of laboratory normal

               -  Total bilirubin <1.5 X upper limit of laboratory normal, unless due to Gilbert's
                  disease

          -  INR <1.5, PT <16 seconds, PTT < 38 seconds

          -  Ability to give informed consent and comply with the protocol

          -  Anticipated lifespan >12 weeks

          -  Women of childbearing potential: negative serum/urine pregnancy test <96 hours prior
             to start of study

          -  Males and women of childbearing potential: must agree to take appropriate precautions
             to avoid pregnancy during treatment and through 90 days after last dose of IP

        Exclusion Criteria:

          -  Involvement in the planning and/or conduct of the study (applies to both
             AstraZeneca/MedImmune staff and/or staff at the study site)

          -  Concurrent enrollment in another clinical study, unless it is an observational
             (non-interventional) clinical study or during the follow-up period of an
             interventional study

          -  Receipt of any investigational anticancer therapy during the last 28 days or 5
             half-lives, whichever is shorter, prior to the first dose of study treatment

          -  Any concurrent chemotherapy, investigational agent, biologic, or hormonal therapy for
             cancer treatment -- concurrent use of hormonal therapy for non-cancer-related
             conditions (e.g., hormone replacement therapy) is acceptable.

          -  Local treatment of isolated lesions for palliative intent is acceptable (e.g., local
             surgery or radiotherapy). -Radiotherapy treatment to more than 30% of the bone marrow
             or with a wide field of radiation within 4 weeks of the first dose of study drug.
             Note: Local treatment of isolated lesions, excluding target lesions, for palliative
             intent is acceptable. -Major surgical procedure (as defined by the Investigator)
             within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions
             for palliative intent is acceptable. -History of allogenic organ transplantation.

          -  Uncontrolled intercurrent illness, including but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, unstable cardiac arrhythmia, interstitial lung disease, serious
             chronic gastrointestinal conditions associated with diarrhea, or psychiatric
             illness/social situations that would limit compliance with study requirement,
             substantially increase risk of incurring AEs, or compromise the ability of the patient
             to give written informed consent -History of another primary malignancy except for:

               -  Malignancy treated with curative intent and with no known active disease ≥1.5
                  years before the first dose of investigational product and of low potential risk
                  for recurrence

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               -  Adequately treated carcinoma in situ without evidence of disease -History of
                  leptomeningeal carcinomatosis -Untreated central nervous system (CNS) metastases
                  and/or carcinomatous meningitis. Note: patients whose brain metastases have been
                  treated may participate provided they show radiographic stability (imaging at
                  least four weeks apart showing no evidence of intracranial progression). In
                  addition, any neurologic symptoms that developed either as a result of the brain
                  metastases or their treatment must have resolved or be stable either without the
                  use of steroids or are stable on a steroid dose of ≤10mg/day of prednisone or its
                  equivalent and anti-seizure medications for at least 14 days prior to the start
                  of treatment. Patients on a stable dose of seizure medicines for epilepsy
                  unrelated to cancer are eligible for the trial.

          -  Active or recent history of diverticulitis. Note: Patients with known diverticulosis
             are permitted to enroll.

          -  History of active primary immunodeficiency. -Active infection, including tuberculosis
             (clinical evaluation that includes clinical history, physical examination, and
             radiographic findings, and TB testing in line with local practice); hepatitis B (known
             positive HBV surface antigen (HBsAg) result); hepatitis C; or human immunodeficiency
             virus (positive HIV 1/2 antibodies). Note: patients with a past or resolved HBV
             infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence
             of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible
             only if polymerase chain reaction is negative for HCV RNA. Patients with treated HIV,
             as evidenced by stable CD4 > 200 for at least 6 months, are eligible. -Current or
             prior use of immunosuppressive medication within 14 days before the first dose of
             study drug. The following are exceptions to this criterion: • Intranasal, inhaled,
             topical steroids, or local steroid injections (e.g., intra articular injection)

             • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone
             or its equivalent

          -  Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease [e.g., colitis or Crohn's disease]; diverticulitis [with
             the exception of diverticulosis]; systemic lupus erythematosus; Sarcoidosis syndrome;
             or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
             arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
             criterion:

               -  Patients with vitiligo or alopecia • Patients with hypothyroidism (e.g.,
                  following Hashimoto syndrome) stable on hormone replacement • Any chronic skin
                  condition that does not require systemic therapy • Patients without active
                  disease in the last 5 years may be included but only after consultation with the
                  study physician • Patients with celiac disease controlled by diet alone -Receipt
                  of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
                  Patients, if enrolled, should not receive live vaccine whilst receiving IP and up
                  to 30 days after the last dose of IP -Known allergy or hypersensitivity to study
                  drug(s) or compounds of similar biologic composition to the study drug(s), or any
                  of the study drug excipients. -Any unresolved NCI CTCAE Grade ≥2 toxicities from
                  prior anti-cancer therapy with the exception of vitiligo, alopecia, and the
                  laboratory values defined in the inclusion criteria. -Patients with Grade ≥2
                  neuropathy will be evaluated on a case-by-case basis after consultation with the
                  Study Physician. -Patients with irreversible toxicity not reasonably expected to
                  be exacerbated by study treatment may be included only after consultation with
                  the Study Physician
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Activation of immune response
Time Frame:28 days
Safety Issue:
Description:The primary objective of this phase Ib clinical trial is to ascertain if there is a difference in immune activation comparing a single dose of MEDI0562 with the equivalent dose divided into a Monday, Wednesday Friday schedule in patients with advanced HNSCC or melanoma. Immune activation will be assessed as a cumulative suppressive index (CSI).

Secondary Outcome Measures

Measure:Cancer-related clinical outcomes (progression free survival)
Time Frame:5 years
Safety Issue:
Description:Cancer-related clinical outcomes in patients receiving MEDI0562 will be compared with historical controls for progression free survival.
Measure:Cancer-related clinical outcomes (overall survival)
Time Frame:5 years
Safety Issue:
Description:Cancer-related clinical outcomes in patients receiving MEDI0562 will be compared with historical controls for overall survival.
Measure:Incidence of Treatment-Emergent Adverse Events in patients with HNSCC or melanoma treated with MEDI0562 (Safety & Tolerability)
Time Frame:5 years
Safety Issue:
Description:The safety of MEDI0562 administration in patients with locally advanced HNSCC and melanoma will be monitored using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Measure:Surgical complications after MEDI0562
Time Frame:28 days
Safety Issue:
Description:Surgical complications after MEDI0562 administration will be monitored using the Clavien-Dindo grading system.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Providence Health & Services

Trial Keywords

  • immunotherapy
  • OX40
  • antibodies
  • HNSCC
  • melanoma
  • phase 1
  • squamous cell

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