Clinical Trials /

Neoadjuvant Atezolizumab in Surgically Resectable Advanced Cutaneous Squamous Cell Carcinoma

NCT04710498

Description:

The purpose of this research is to evaluate whether the administration of atezolizumab before surgical resection of your tumor is feasible and to evaluate the treatment response, safety, and tolerability of atezolizumab.

Related Conditions:
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Atezolizumab in Surgically Resectable Advanced Cutaneous Squamous Cell Carcinoma
  • Official Title: ML42362: Neoadjuvant Atezolizumab in Surgically Resectable Advanced Cutaneous Squamous Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: IRB-59070
  • SECONDARY ID: ENT0082
  • NCT ID: NCT04710498

Conditions

  • Cutaneous Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
AtezolizumabRO5541267Atezolizumab

Purpose

The purpose of this research is to evaluate whether the administration of atezolizumab before surgical resection of your tumor is feasible and to evaluate the treatment response, safety, and tolerability of atezolizumab.

Detailed Description

      Primary Objective:

      Determine the feasibility of three doses of atezolizumab prior to surgery in patients with
      advanced cutaneous squamous cell carcinoma

      Secondary Objectives:

        -  Assess response rates to neoadjuvant atezolizumab Objective response rate following
           completion of neoadjuvant therapy based on RECIST 1.1 criteria oPathological response
           rate (major and complete pathological response) in final surgical resection specimen

        -  Assess change in surgical margins or vital structures preserved following neoadjuvant
           treatment

        -  Assess safety and tolerability of neoadjuvant atezolizumab
    

Trial Arms

NameTypeDescriptionInterventions
AtezolizumabExperimentalSubjects will receive neoadjuvant atezolizumab intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 (+/- 3 days) of each 21-day cycle for a total of 3 doses prior to surgery, unless there is clinical or radiographic evidence of disease progression.
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Signed Informed Consent Form

          2. Age ³ 18 years at time of signing Informed Consent Form

          3. Histologically or cytologically confirmed squamous cell carcinoma

          4. Measurable disease per RECIST v1.1

               -  Note that protocol specified imaging is not necessary to fulfill this criterion.
                  For example, a patient presenting with a visible 4cm primary lesion who has
                  obviously RECIST evaluable disease may be considered eligible prior to baseline
                  imaging stipulated in the protocol.

          5. Availability of a representative tumor specimen that is suitable for determination of
             PD-L1 immunohistochemical stain evaluation.

          6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          7. Adequate hematologic and end-organ function appropriate for surgery as determined by
             routine preoperative evaluation. If liver function, renal function and hematologic
             laboratory test results are within limits acceptable for elective surgery. Laboratory
             results that will need to be obtained within 28 days prior to initiation of study
             treatment:

               -  aspartate aminotransferase (AST), alanine aminotransferas (ALT), total bilirubin,
                  and alkaline phosphatase (ALP) £ 2.5 x upper limit of normal (ULN.).

               -  Thyroid-stimulating hormone (TSH) < 13, Patients with a history of a high TSH who
                  are receiving levothyroxine replacement at the time of eligibility evaluation and
                  have no clinical evidence of hypothyroidism are eligible.

          8. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen

          9. Negative hepatitis B surface antigen (HBsAg) test at screening

         10. For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive methods, as defined below: Women must
             remain abstinent or use contraceptive methods with a failure rate of < 1% per year
             during the treatment period and for 5 months after the final dose of atezolizumab.

             A woman is considered to be of childbearing potential if she is postmenarchal, has not
             reached a postmenopausal state (³ 12 continuous months of amenorrhea with no
             identified cause other than menopause), and has not undergone surgical sterilization
             (removal of ovaries and/or uterus). The definition of childbearing potential may be
             adapted for alignment with local guidelines or requirements.

             Examples of contraceptive methods with a failure rate of < 1% per year include
             bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit
             ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.

             The reliability of sexual abstinence should be evaluated in relation to the duration
             of the clinical trial and the preferred and usual lifestyle of the patient. Periodic
             abstinence (e.g., calendar, ovulation, symptothermal, or postovulation

         11. For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use
             a condom, and agreement to refrain from donating sperm, as defined below:

        With a female partner of childbearing potential or pregnant female partner, men must agree
        to remain abstinent or use a condom during the treatment period and for 5 months after the
        final dose of atezolizumab to avoid exposing the embryo. Men must agree to refrain from
        donating sperm during this same period

        Exclusion Criteria:

          1. Patients not eligible for standard of care surgical resection

          2. Distant metastatic disease

          3. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (once monthly or more frequently)

               -  Patients with indwelling catheters (e.g., PleurX are allowed.

          4. Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12
             mg/dL or corrected serum calcium > ULN)

          5. Active or history of autoimmune disease or immune deficiency, including, but not
             limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
             antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome,
             or multiple sclerosis (see Appendix G for a more comprehensive list of autoimmune
             diseases and immune deficiencies), with the following exceptions: ·Patients with a
             history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone
             are eligible for the study.

             ·Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are
             eligible for the study.

             ·Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
             dermatologic manifestations only (e.g., patients with psoriatic arthritis are
             excluded) are eligible for the study provided all of following conditions are met:

               -  Rash must cover < 10% of body surface area

               -  Disease is well controlled at baseline and requires only low-potency topical
                  corticosteroids

               -  No occurrence of acute exacerbations of the underlying condition requiring
                  psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents,
                  oral calcineurin inhibitors, or high-potency or oral corticosteroids within the
                  previous 12 months

          6. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
             obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
             active pneumonitis on screening chest computed tomography (CT) scan ·History of
             radiation pneumonitis in the radiation field (fibrosis) is permitted.

        7 .Active tuberculosis. Patents do NOT have to be screened for tuberculosis for this trial.

        8. Significant cardiovascular disease (such as New York Heart Association Class II or
        greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3
        months prior to initiation of study treatment, unstable arrhythmia, or unstable angina 9.
        Severe infection within 4 weeks prior to initiation of study treatment, including, but not
        limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
        10. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of
        study treatment

          -  Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract
             infection or chronic obstructive pulmonary disease exacerbation) are eligible for the
             study. 11. Prior allogeneic stem cell or solid organ transplantation 12. Any other
             disease, metabolic dysfunction, physical examination finding, or clinical laboratory
             finding that contraindicates the use of an investigational drug, may affect the
             interpretation of the results, or may render the patient at high risk from treatment
             complications 13. Treatment with a live, attenuated vaccine within 4 weeks prior to
             initiation of study treatment, or anticipation of need for such a vaccine during
             atezolizumab treatment or within 5 months after the final dose of atezolizumab 14.
             Current treatment with anti-viral therapy for hepatitis B virus (HBV) 15. Treatment
             with investigational therapy within 28 days prior to initiation of study treatment 16.
             Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
             anti- cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), anti-PD-1, and anti-PD-L1
             therapeutic antibodies 17. Treatment with systemic immunostimulatory agents
             (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or
             5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
             18. Treatment with systemic immunosuppressive medication (including, but not limited
             to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
             anti-tumor necrosis factor (TNF)-a agents) within 2 weeks prior to initiation of study
             treatment, or anticipation of need for systemic immunosuppressive medication during
             study treatment, with the following exceptions:

          -  Patients who received acute, low-dose systemic immunosuppressant medication or a
             one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of
             corticosteroids for a contrast allergy) are eligible for the study has been obtained.

          -  Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for
             chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids
             for orthostatic hypotension or adrenal insufficiency are eligible for the study. 19.
             History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
             or fusion proteins 20. Known hypersensitivity to Chinese hamster ovary cell products
             or to any component of the atezolizumab formulation 21. Pregnancy or breastfeeding, or
             intention of becoming pregnant during study treatment or within 5 months after the
             final dose of study treatment

          -  Women of childbearing potential must have a negative serum pregnancy test result
             within 14 days prior to initiation of study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of patients who complete neoadjuvant therapy and surgical resection
Time Frame:1 Day
Safety Issue:
Description:Percentage of patients that are able to complete 3 cycles of neoadjuvant neoadjuvant atezolizumab, followed by surgical resection will be measured.

Secondary Outcome Measures

Measure:Objective response rate
Time Frame:After cycle 3 (duration of each cycle 21 days)
Safety Issue:
Description:Objective response rate will be measured based on RECIST v1.1 criteria at baseline, after cycle 2, and at the time or surgery
Measure:Pathological response rate
Time Frame:After cycle 3 (duration of each cycle 21 days)
Safety Issue:
Description:Pathological response will be assessed by local pathological review at baseline, after cycle 2, and and at the time or surgery Patients with no viable tumor seen will be classified as a complete pathological response. Patients with < 10% of viable tumor will be classified as a major pathological response.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Stanford University

Last Updated

January 14, 2021