Clinical Trials /

Cemiplimab in Treating Participants With Recurrent Stage III-IV Head and Neck Squamous Cell Cancer Before Surgery

NCT03565783

Description:

This phase II trial studies how well cemiplimab works before surgery in treating participants with stage III-IV head and neck squamous cell cancer that has come back. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Cemiplimab in Treating Participants With Recurrent Stage III-IV Head and Neck Squamous Cell Cancer Before Surgery
  • Official Title: Phase II Study of REGN2810 Prior to Surgery in Patients With Advanced-Stage, Resectable Cutaneous Squamous Cell Carcinoma of the Head and Neck

Clinical Trial IDs

  • ORG STUDY ID: 2017-0332
  • SECONDARY ID: NCI-2018-01313
  • SECONDARY ID: 2017-0332
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03565783

Conditions

  • Advanced Head and Neck Squamous Cell Carcinoma
  • Recurrent Head and Neck Squamous Cell Carcinoma
  • Resectable Head and Neck Squamous Cell Carcinoma
  • Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
  • Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8

Interventions

DrugSynonymsArms
CemiplimabREGN2810Treatment (cemiplimab)

Purpose

This phase II trial studies how well cemiplimab works before surgery in treating participants with stage III-IV head and neck squamous cell cancer that has come back. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the overall response rate (ORR) using Response Evaluation Criteria in Solid
      Tumors (RECIST) version (v)1.1 criteria to neoadjuvant cemiplimab (REGN2810) (anti-PD-1
      inhibitor) in patients with advanced-stage cutaneous squamous cell carcinoma (cSCC) of the
      head and neck who are planned for definitive local surgery and radiation.

      SECONDARY OBJECTIVES:

      I. To determine the pathologic response rate to neoadjuvant REGN2810 in patients with
      advanced-stage cSCC of the head and neck.

      II. To determine the safety and tolerability of neoadjuvant REGN2810 in patients with
      advanced-stage cSCC of the head and neck who are planned for definitive local surgery and
      radiation.

      III. To estimate the 2-year disease-specific (DSS), disease-free (DFS) and overall survival
      (OS) compared to historical controls.

      IV. To determine the time to recurrence and patterns of failure. V. To evaluate the effects
      of neoadjuvant REGN2810 on the expression of PD-1 and potential related immune regulating
      targets in cSCC of the head and neck.

      OUTLINE:

      Participants receive cemiplimab intravenously (IV) over 30 minutes every 3 weeks. Courses
      repeat every 3 weeks for up to 6 weeks in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, participants are followed up for 30 days and then
      periodically for up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (cemiplimab)ExperimentalParticipants receive cemiplimab IV over 30 minutes every 3 weeks. Courses repeat every 3 weeks for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
  • Cemiplimab

Eligibility Criteria

        Inclusion Criteria:

          -  Biopsy-proven, primary or recurrent advanced-stage (III/IV) cutaneous squamous cell
             carcinoma of the head and neck.

          -  Surgical resection must be planned as primary therapy with expected adjuvant radiation
             therapy. Patients are eligible with previous surgical intervention if they have
             residual or recurrent disease, and it is greater than 4 weeks since surgery and they
             have fully recovered from surgery.

          -  Signed informed consent form (ICF).

          -  Ability and willingness to comply with the requirements of the study protocol.

          -  Absolute neutrophil count (ANC) >= 1500 cells/uL (obtained within 4 weeks [+/-3 days]
             prior to study entry).

          -  White blood cell (WBC) counts >= 2500/uL (obtained within 4 weeks [+/-3 days] prior to
             study entry).

          -  Lymphocyte count >= 300/uL (obtained within 4 weeks [+/-3 days] prior to study entry).

          -  Platelet count >= 100,000uL for patients with hematologic malignancies, platelet count
             >= 75,000/uL (obtained within 4 weeks [+/-3 days] prior to study entry).

          -  Hemoglobin >= 9.0 g/dL (obtained within 4 weeks [+/-3 days] prior to study entry).

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) with the following exception:
             patients with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be
             enrolled (obtained within 4 weeks [+/-3 days] prior to study entry).

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN
             (obtained within 4 weeks [+/-3 days] prior to study entry).

          -  Alkaline phosphatase =< 2.5 x ULN with the following exception: patients with
             documented bone metastases: alkaline phosphatase =< 5 x ULN (obtained within 4 weeks
             [+/-3 days] prior to study entry).

          -  Serum creatinine =< 1.5 x ULN or creatinine clearance >= 50 mL/min on the basis of the
             Cockcroft-Gault glomerular filtration rate estimation (obtained within 4 weeks [+/-3
             days] prior to study entry).

          -  Measurable disease per RECIST v1.1 and/or per direct clinical measurements for primary
             tumors upon a variance between clinical and radiographic evaluation.

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

          -  International normalized ratio (INR) and activated partial thromboplastin time (aPTT)
             =< 1.5 x ULN (This applies only to patients who do not receive therapeutic
             anticoagulation; patients receiving therapeutic anticoagulation [such as
             low-molecular-weight heparin or warfarin] should be on a stable dose.)

          -  No evidence of distant metastases and measurable disease (> 1.5 cm).

        Exclusion Criteria:

          -  Any approved anticancer therapy, including chemotherapy, hormonal therapy, or
             radiotherapy, within 3 weeks prior to initiation of study treatment; however, the
             following are allowed: Hormone-replacement therapy; palliative radiotherapy for bone
             metastases > 2 weeks prior to cycle 1, day 1.

          -  Adverse events (AEs) from prior anticancer therapy that have not resolved to grade =<
             1 except for alopecia.

          -  Bisphosphonate therapy for symptomatic hypercalcemia (use of bisphosphonate therapy
             for other reasons [e.g., osteoporosis] is allowed.)

          -  Patients with acute leukemias, accelerated/blast phase chronic myelogenous leukemia,
             chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory
             myeloma.

          -  Pregnancy, lactation, or breastfeeding.

          -  Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies.

          -  Inability to comply with study and follow-up procedures.

          -  History or risk of autoimmune disease, including but not limited to systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
             associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's
             syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune
             thyroid disease, vasculitis, or glomerulonephritis. Patients with a history of
             autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be
             eligible. Patients with controlled type 1 diabetes mellitus on a stable insulin
             regimen may be eligible.

          -  Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with
             dermatologic manifestations only (e.g., patients with psoriatic arthritis would be
             excluded) are permitted provided that they meet the following conditions: Patients
             with psoriasis must have a baseline ophthalmologic exam to rule out ocular
             manifestations; Rash must cover less than 10% of body surface area (BSA); Disease is
             well controlled at baseline and only requiring low potency topical steroids (e.g.,
             hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%,
             alclometasone dipropionate 0.05%); No acute exacerbations of underlying condition
             within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA],
             methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or
             oral steroids).

          -  History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
             organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
             pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
             tomography (CT) scan. (History of radiation pneumonitis in the radiation field
             [fibrosis] is permitted.)

          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that may affect the
             interpretation of the results or render the patient at high risk from treatment
             complications.

          -  History of human immunodeficiency virus (HIV) infection or active hepatitis B (chronic
             or acute) or hepatitis C infection. (Patients with past or resolved hepatitis B
             infection; defined as having a negative hepatitis B surface antigen [HBsAg] test and a
             positive anti-HBc [antibody to hepatitis B core antigen] antibody test, are eligible.
             Patients positive for hepatitis C virus [HCV] antibody are eligible only if polymerase
             chain reaction [PCR] is negative for HCV ribonucleic acid [RNA].)

          -  Active tuberculosis.

          -  Severe infections within 4 weeks prior to cycle 1, day 1, including but not limited to
             hospitalization for complications of infection, bacteremia, or severe pneumonia.

          -  Signs or symptoms of infection as determined by the treating team within 2 weeks prior
             to cycle 1, day 1.

          -  Received oral or IV antibiotics within 2 weeks prior to cycle 1, day 1 (Patients
             receiving prophylactic antibiotics [e.g., for prevention of a urinary tract infection
             or chronic obstructive pulmonary disease] are eligible.)

          -  Major surgical procedure within 28 days prior to cycle 1, day 1.

          -  Administration of a live, attenuated vaccine within 4 weeks before cycle 1, day 1 or
             anticipation that such a live, attenuated vaccine will be required during the study.
             (Influenza vaccination should be given during influenza season only [approximately
             October to March]. Patients must not receive live, attenuated influenza vaccine [e.g.,
             FluMist] within 4 weeks prior to cycle 1, day 1 or at any time during the study.)

          -  Malignancies other than the disease under study within 5 years prior to cycle 1, day
             1, with the exception of those with a negligible risk of metastasis or death and with
             expected curative outcome (such as adequately treated carcinoma in situ of the cervix,
             basal or squamous cell skin cancer, localized prostate cancer treated surgically with
             curative intent, or ductal carcinoma in situ treated surgically with curative intent)
             or undergoing active surveillance per standard-of-care management (e.g., chronic
             lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score =< 6, and
             prostate-specific antigen [PSA] =< 10 mg/mL, etc.)

          -  Continued sexual activity in men** or women of childbearing potential*** who are
             unwilling to practice highly effective contraception during the study and until 6
             months after the last dose of study drug (highly effective contraceptive measures
             include stable use of oral contraceptives such as combined estrogen and progestogen
             and progestogen only hormonal contraception or other prescription pharmaceutical
             contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device
             [IUD]; intrauterine hormone-releasing system [IUS]; bilateral tubal ligation;
             vasectomy, and sexual abstinence). (**Contraception is not required for men with
             documented vasectomy ***Postmenopausal women must be amenorrheic for at least 12
             months in order not to be considered of childbearing potential. Pregnancy testing and
             contraception are not required for women with documented hysterectomy or tubal
             ligation.)

          -  Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway
             targeting agents. Patients who have received prior treatment with anti-CTLA-4 may be
             enrolled, provided the following requirements are met: Minimum of 12 weeks from the
             first dose of anti-CTLA-4 and > 6 weeks from the last dose. No history of severe
             immune-related adverse effects from anti-CTLA 4 (National Cancer Institute [NCI]
             Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4).

          -  Treatment with systemic immunostimulatory agents (including but not limited to
             interferon [IFN] or interleukin [IL]-2) within 6 weeks or five half-lives of the drug
             (whichever is shorter) prior to cycle 1, day 1.

          -  Treatment with investigational agent within 4 weeks prior to cycle 1, day 1 (or within
             five half lives of the investigational product, whichever is longer).

          -  Treatment with systemic immunosuppressive medications (including but not limited to
             prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor
             necrosis factor [anti-TNF] agents) within 2 weeks prior to cycle 1, day 1. (Patients
             who have received acute, low dose, systemic immunosuppressant medications [e.g., a
             one-time dose of dexamethasone for nausea] may be enrolled. The use of inhaled
             corticosteroids and mineralocorticoids [e.g., fludrocortisone] for patients with
             orthostatic hypotension or adrenocortical insufficiency is allowed.)

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins.

          -  Patients with prior allogeneic bone marrow transplantation or prior solid organ
             transplantation.

          -  Patients with prior treatment with idelalisib.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
Time Frame:Up to 6 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Time to recurrence
Time Frame:Up to 5 years
Safety Issue:
Description:The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Measure:Patterns of failure
Time Frame:Up to 5 years
Safety Issue:
Description:Summary statistics will be provided for continuous variables.
Measure:Disease-specific survival
Time Frame:Up to 2 years
Safety Issue:
Description:Frequency tables will be used to summarize categorical variables.
Measure:Disease-free survival
Time Frame:Up to 5 years
Safety Issue:
Description:The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Measure:Overall survival
Time Frame:Up to 5 years
Safety Issue:
Description:The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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