Cutaneous Squamous Cell Carcinoma
Conditions
Brief summary
The purpose of this research is to evaluate whether the administration of atezolizumab before surgical resection of the 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 * Pathological 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
Interventions
DRUGAtezolizumab
Atezolizumab administered intravenous (IV) infusion at a fixed dose of 1200 mg
Sponsors
Genentech, Inc.
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed Informed Consent Form 2. Age ≥ 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-L 1 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.
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, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, etc. 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-lymphocyteassociated protein 4 (CTLA-4 ), anti-PD-1, and anti-PD-L 1 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:
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Complete Neoadjuvant Therapy and Were Eligible for Curative Surgical Resection | 9 weeks | Percentage of patients that are able to complete 3 cycles of neoadjuvant atezolizumab and were eligible for curative surgical resection will be measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | After cycle 3 (duration of each cycle 21 days) | Objective response rate will be measured based on RECIST v1.1 criteria at baseline, after cycle 2, and at the time or surgery. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of diameters of all target lesions; Progressive Disease (PD), at least a 20% increase in the sum of diameters of target lesions; Overall Response (OR) = CR + PR. |
| Pathological Response Rate | After cycle 3 (duration of each cycle 21 days) | 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. |
| Changes in Vital Structures | 9 weeks | Assessed changes in vital structures preserved following neoadjuvant treatment |
| Changes in Surgical Margins | 9 weeks | Assess change in surgical margins preserved following neoadjuvant treatment |
| Safety and Tolerability of Neoadjuvant Atezolizumab | 9 weeks | A secondary outcome measure was to assess safety and tolerability of neoadjuvant atezolizumab. Adverse events (AE), serious adverse events (SAE), and treatment-related toxicities were recorded at each study-related visit. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atezolizumab Subjects received a 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: Atezolizumab administered intravenous (IV) infusion at a fixed dose of 1200 mg | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Atezolizumab |
|---|---|
| Age, Customized 18 to 29 years | 0 Participants |
| Age, Customized 30 to 39 years | 0 Participants |
| Age, Customized 40 to 49 years | 0 Participants |
| Age, Customized 50 to 59 years | 2 Participants |
| Age, Customized 60 to 69 years | 6 Participants |
| Age, Customized 70 to 79 years | 8 Participants |
| Age, Customized 80 to 89 years | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 1 / 20 |
Outcome results
Primary
Percentage of Patients Who Complete Neoadjuvant Therapy and Were Eligible for Curative Surgical Resection
Percentage of patients that are able to complete 3 cycles of neoadjuvant atezolizumab and were eligible for curative surgical resection will be measured.
Time frame: 9 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Atezolizumab | Percentage of Patients Who Complete Neoadjuvant Therapy and Were Eligible for Curative Surgical Resection | 16 Participants |
Secondary
Changes in Surgical Margins
Assess change in surgical margins preserved following neoadjuvant treatment
Time frame: 9 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atezolizumab | Changes in Surgical Margins | Microscopically positive margins | 1 Participants |
| Atezolizumab | Changes in Surgical Margins | Microscopically negative margins | 18 Participants |
Secondary
Changes in Vital Structures
Assessed changes in vital structures preserved following neoadjuvant treatment
Time frame: 9 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atezolizumab | Changes in Vital Structures | Smaller surgical resection | 10 Participants |
| Atezolizumab | Changes in Vital Structures | Larger surgical resection | 1 Participants |
Secondary
Objective Response Rate
Objective response rate will be measured based on RECIST v1.1 criteria at baseline, after cycle 2, and at the time or surgery. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of diameters of all target lesions; Progressive Disease (PD), at least a 20% increase in the sum of diameters of target lesions; Overall Response (OR) = CR + PR.
Time frame: After cycle 3 (duration of each cycle 21 days)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atezolizumab | Objective Response Rate | Complete response | 1 Participants |
| Atezolizumab | Objective Response Rate | Partial response | 7 Participants |
| Atezolizumab | Objective Response Rate | Stable disease | 10 Participants |
| Atezolizumab | Objective Response Rate | Disease progression | 1 Participants |
| Atezolizumab | Objective Response Rate | No imaging | 1 Participants |
Secondary
Pathological Response Rate
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.
Time frame: After cycle 3 (duration of each cycle 21 days)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atezolizumab | Pathological Response Rate | Pathological complete response (no viable tumor cells) | 7 Participants |
| Atezolizumab | Pathological Response Rate | Pathological major response (<= 10% viable tumor cells) | 4 Participants |
| Atezolizumab | Pathological Response Rate | No pathological response (>10% viable tumor cells) | 8 Participants |
| Atezolizumab | Pathological Response Rate | No pathological evaluation (surgery declined) | 1 Participants |
Secondary
Safety and Tolerability of Neoadjuvant Atezolizumab
A secondary outcome measure was to assess safety and tolerability of neoadjuvant atezolizumab. Adverse events (AE), serious adverse events (SAE), and treatment-related toxicities were recorded at each study-related visit.
Time frame: 9 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atezolizumab | Safety and Tolerability of Neoadjuvant Atezolizumab | AE's (patients affected) | 20 Participants |
| Atezolizumab | Safety and Tolerability of Neoadjuvant Atezolizumab | SAE's (patients affected) | 1 Participants |