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Neoadjuvant Atezolizumab in Surgically Resectable Advanced Cutaneous Squamous Cell Carcinoma
Trial ID: NCT04710498
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.
ML42362: Neoadjuvant Atezolizumab in Surgically Resectable Advanced Cutaneous Squamous Cell Carcinoma
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
- 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
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
- 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
- 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.
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