| Eligibility |
Inclusion Criteria:
- Histologically or cytologically confirmed locally advanced borderline resectable or
unresectable cSCC and oligometastatic (1-3 sites of metastatic disease) cSCC receiving
therapy to the primary
- Measurable disease defined as lesions that can be accurately measured in at least one
dimension (longest diameter to be recorded) as > 10 mm with computed tomography (CT)
scan or > 10 mm with calipers by clinical exam by Response Evaluation Criteria in
Solid Tumors (RECIST) 1.1
- Written informed consent and any locally-required authorization (e.g., Health
Insurance Portability and Accountability Act [HIPAA] in the United States of America
[USA], European Union [EU] Data Privacy Directive in the EU) obtained from the patient
prior to performing any protocol-related procedures, including screening evaluations
- Age >= 18 years at time of study entry
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- Life expectancy >= 24 weeks
- Body weight > 30 kg
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1.0 x 10^9/L (>= 1000 per mm^3)
- Platelet count >= 75 x 10^9/L (>= 75,000 per mm^3)
- Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). This will not
apply to patients with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or
hepatic pathology), who will be allowed only in consultation with their physician
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal
- Serum albumin 25 g/L (2.5 g/dL)
- Measured creatinine clearance (CL) > 40 mL/min or calculated creatinine CL>40 mL/min
by the Cockcroft-Gault formula or by 24-hour urine collection for determination of
creatinine clearance
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients. Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:
- Women < 50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy)
- Women >= 50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses > 1 year ago, had
chemotherapy-induced menopause with last menses > 1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
hysterectomy)
- Patient 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 3 months
- Patients with active interstitial lung disease (ILD)/pneumonitis or with a history of
ILD/pneumonitis requiring steroids
- Concurrent enrolment in another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study
- Any previous treatment with a PD1 or PD-L1 inhibitor, including atezolizumab,
anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)
antibody (including ipilimumab or any other antibody or drug specifically targeting
T-cell co-stimulation or checkpoint pathways)
- 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
- Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine
therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
antibodies, other investigational agent) 30 days prior to the first dose of study drug
for patients who have received prior tyrosine kinase inhibitors (TKIs) [e.g.,
erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin
C. (If sufficient wash-out time has not occurred due to the schedule or
pharmacokinetics (PK) properties of an agent, a longer wash-out period may be
required.)
- Patients with corrected QT (QTc) interval > 470 msec during screening
- Current or prior use of immunosuppressive medication within 14 days (use 28 days if
combining atezolizumab with a novel agent) before the first dose of atezolizumab, 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. 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
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
- Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal
therapy that is not part of standard National Comprehensive Cancer Network (NCCN)
indicated head and neck squamous cell carcinoma (HNSCC) adjuvant concurrent
chemoradiotherapy (CRT). Concurrent use of hormonal therapy for non-cancer-related
conditions (e.g., hormone replacement therapy) is acceptable
- History of allogenic organ or bone marrow transplantation
- 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
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, idiopathic pulmonary fibrosis,
organizing pneumonia, uncontrolled pleural effusion, pericardial effusion, or ascites
requiring recurrent drainage procedures (once monthly or more frequently),
uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12
mg/dL or corrected serum calcium ULN), uncontrolled tumor-related pain, uncontrolled
hypertension, unstable angina pectoris, 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 adverse events (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 >= 3
years before the first dose of IP 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 active primary immunodeficiency
- Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and tuberculosis (TB) testing
in line with local practice), hepatitis B (known positive hepatitis B virus [HBV]
surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus
(positive human immunodeficiency virus [HIV] 1/2 antibodies). 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 virus
(HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
- 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 atezolizumab
and up to 5 months after the last dose of atezolizumab
- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ highly effective birth control
from screening to 5 months after the last dose of atezolizumab monotherapy. Patient
must have a negative serum pregnancy test within 72 hours of study entry
- Known hypersensitivity to Chinese hamster ovary cell products or to any component of
the atezolizumab formulation
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
or fusion proteins
- Prior randomization or treatment in a previous atezolizumab clinical study
- Judgment by the investigator that the patient is unsuitable to participate in the
study and the patient is unlikely to comply with study procedures, restrictions and
requirements
|
