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A PD-1 Checkpoint Inhibitor (Cemiplimab) for High-Risk Localized, Locally Recurrent, or Regionally Advanced Skin Cancer

Primary Purpose

Recurrent Skin Squamous Cell Carcinoma, Resectable Skin Squamous Cell Carcinoma, Stage I Skin Cancer

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cemiplimab
Resection
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Skin Squamous Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed, cutaneous squamous cell carcinoma
  • Patients must have disease that is deemed potentially resectable, at the time of the start of study, by the treating investigator. The decision to perform surgery on patients must be based on good clinical judgment. Eligible patients for surgical resection must have disease that, in the judgment of the surgeon, is deemed potentially resectable, resulting in free surgical margins
  • Patients must have measurable disease
  • Patients must have disease that is considered either: (1) high-risk localized CSCC, (2) locally recurrent CSCC, or (3) regionally advanced CSCC. The criteria specific to each of these populations is listed below

    • For patients with high-risk localized CSCC, at least two of the following clinical or pathologic high-risk features must be present to be eligible:

      • Clinical risk factors

        • Any tumor size > 2.0 cm in diameter
        • Tumors > 1.0 cm in high risk locations, including "mask areas" (central face, eyelids, eyebrow, nose, lips [cutaneous], periorbital, chin, mandible, preauricular and postauricular skin/sulci, genitalia, hands, feet, cheek, forehead, scalp, neck and pretibial)
        • Any rapidly growing and/or symptomatic tumor
      • Pathologic risk factors

        • Poorly differentiated histology
        • Depth > 6 mm in thickness
        • Acantholytic / adenoid, adenosquamous, desmoplastic, or metaplastic / carcinosarcomatous histologic subtypes
        • Invasion beyond subcutaneous fat
        • Perineural, lymphatic, or vascular involvement
    • Patients with locally recurrent CSCC, that failed prior surgery, radiation or systemic therapy, are eligible, as long as they have measurable disease and are deemed potentially resectable by the treating investigator
    • Patients with regionally advanced CSCC, including in-transit, cutaneous, subcutaneous or lymph node metastases are eligible, as long as they have measurable disease and are deemed potentially resectable by the treating investigator
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count >= 1,000 /mcL
  • Absolute lymphocyte count >= 500 / mcL
  • Hemoglobin >= 8.0 g/dL
  • Platelets >= 75,000/mcl
  • Total bilirubin =< 1.5 x institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SPGT]) =< 3 x institutional upper limit of normal
  • Creatinine =< 1.8 mg/dl
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

    • Has not undergone a hysterectomy or bilateral oophorectomy; or
    • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
  • Ability to understand and the willingness to sign a written informed consent and comply with surgical resection at end of study and other study-related procedures

Exclusion Criteria:

  • Metastatic disease that is unresectable. Patients with visceral metastases are not eligible. Regionally advanced disease, including in-transit, cutaneous, subcutaneous, or nodal metastases are allowed, if deemed potentially resectable by the investigator
  • Prior treatment with cemiplimab or any other agent that blocks the PD-1 or PD-L1 pathway
  • Prior treatment with other immune modulating agents within fewer than 4 weeks, prior to the first dose of cemiplimab. Examples of immune modulating agents include blockers of CTLA-4, 4-1BB, OX-40, therapeutic vaccines, or cytokine therapies
  • Patients must not be receiving other concomitant biologic therapy, hormonal therapy, chemotherapy, other anti-cancer therapy or any other investigational agents while on this protocol
  • Radiation therapy, non-cytotoxic agents or investigational agents in the 4 weeks prior to registration
  • Immunosuppressive systemic corticosteroids equivalent to prednisone 10 mg or greater in the 14 days prior to the first dose of cemiplimab
  • Any major surgery within 14 days prior to the first dose of cemiplimab. Patients must have recovered from any major complications before registration
  • Active autoimmune disease requiring systemic treatment in the past 2 years (i.e. use of disease modifying agents or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment
  • History of other prior malignancy in the last five years, with the exception of: adequately treated non-melanoma skin cancers (including multiple primary skin cancers), adequately treated in situ cancer, and other local tumors considered cured by local treatment (including melanoma)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cemiplimab or any other PD-1 or PD-L1 inhibitor
  • Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness / social situations that would limit compliance with study requirements
  • Positive pregnancy test, active pregnancy or nursing / breast-feeding, due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
  • History solid organ or bone marrow transplantation

Sites / Locations

  • Los Angeles County-USC Medical CenterRecruiting
  • USC / Norris Comprehensive Cancer CenterRecruiting
  • Hoag Memorial HospitalRecruiting
  • Northwestern University Feinberg School of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (cemiplimab, surgical resection)

Arm Description

Patients receive cemiplimab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles (or up to 4 cycles for patients whose disease is unresectable after 3 cycles) in the absence of disease progression or unacceptable toxicity. Within 6 weeks of last dose of therapy, patients with potentially resectable tumors undergo surgical resection.

Outcomes

Primary Outcome Measures

Confirmed pathologic partial response
Defined by presence of < 50% malignant cells. Descriptive statistics will be used to summarize the measurements.

Secondary Outcome Measures

Pathologic complete response rate
Descriptive statistics will be used to summarize the measurements.
Objective response rate
Measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Descriptive statistics will be used to summarize the measurements.
Progression-free survival
Measured by RECIST v1.1. Descriptive statistics will be used to summarize the measurements.
Incidence of toxicities
All toxicities will be summarized and graded according to maximum grade by Common Terminology Criteria for Adverse Events v4. Descriptive statistics will be used to summarize the measurements.

Full Information

First Posted
March 17, 2020
Last Updated
May 24, 2023
Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04315701
Brief Title
A PD-1 Checkpoint Inhibitor (Cemiplimab) for High-Risk Localized, Locally Recurrent, or Regionally Advanced Skin Cancer
Official Title
Evaluating the PD-1 Checkpoint Inhibitor, Cemiplimab, as Neoadjuvant Therapy in High Risk Localized, Locally Recurrent, and Regionally Advanced Cutaneous Squamous Cell Carcinoma: A Phase II Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 17, 2020 (Actual)
Primary Completion Date
June 17, 2024 (Anticipated)
Study Completion Date
June 17, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies how well cemiplimab before surgery works in treating patients with skin cancer that is high-risk and has not spread to other parts of the body (localized), has come back locally (locally recurrent), or has spread regionally (regionally advanced), and can be removed by surgery (resectable). 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 OBJECTIVE: I. To assess the pathological partial response (PPR) rate in patients with potentially resectable cutaneous squamous cell carcinoma (CSCC) treated with neoadjuvant cemiplimab. SECONDARY OBJECTIVES: I. To estimate the pathological complete response rate (PCR). II. To estimate the Response Evaluation Criteria in Solid Tumors (RECIST) (version [v]1.1) 9 week objective response rate (ORR). III. To estimate the RECIST (v1.1) 12 month progression free (PFS). IV. To assess the toxicity among patients with CSCC treated with neoadjuvant cemiplimab. EXPLORATORY OBJECTIVES: I. To evaluate tumor mutational burden (TMB) and correlate with response to PD-1 blockade therapy. II. To evaluate PD-L1 expression on CSCC tumor cells and correlate with response to PD-1 blockade. III. To evaluate CD8+ T cell infiltration into CSCC tumors and correlate with response to PD-1 blockade. IV. To assess other adaptive immune resistance mechanisms in CSCC tumors. OUTLINE: Patients receive cemiplimab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles (or up to 4 cycles for patients whose disease is unresectable after 3 cycles) in the absence of disease progression or unacceptable toxicity. Within 6 weeks of last dose of therapy, patients with potentially resectable tumors undergo surgical resection. After completion of study treatment, patients are followed up every 3 months for 24 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Skin Squamous Cell Carcinoma, Resectable Skin Squamous Cell Carcinoma, Stage I Skin Cancer, Stage II Skin Cancer, Stage III Skin Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (cemiplimab, surgical resection)
Arm Type
Experimental
Arm Description
Patients receive cemiplimab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles (or up to 4 cycles for patients whose disease is unresectable after 3 cycles) in the absence of disease progression or unacceptable toxicity. Within 6 weeks of last dose of therapy, patients with potentially resectable tumors undergo surgical resection.
Intervention Type
Biological
Intervention Name(s)
Cemiplimab
Other Intervention Name(s)
Cemiplimab RWLC, Cemiplimab-rwlc, Libtayo, REGN2810
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Resection
Other Intervention Name(s)
Surgical Resection
Intervention Description
Undergo surgical resection
Primary Outcome Measure Information:
Title
Confirmed pathologic partial response
Description
Defined by presence of < 50% malignant cells. Descriptive statistics will be used to summarize the measurements.
Time Frame
Up to 24 months after completion of study treatment
Secondary Outcome Measure Information:
Title
Pathologic complete response rate
Description
Descriptive statistics will be used to summarize the measurements.
Time Frame
Up to 24 months after completion of study treatment
Title
Objective response rate
Description
Measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Descriptive statistics will be used to summarize the measurements.
Time Frame
At 9 weeks
Title
Progression-free survival
Description
Measured by RECIST v1.1. Descriptive statistics will be used to summarize the measurements.
Time Frame
From start of treatment to time of progression or death whichever comes first, assessed at 12 months
Title
Incidence of toxicities
Description
All toxicities will be summarized and graded according to maximum grade by Common Terminology Criteria for Adverse Events v4. Descriptive statistics will be used to summarize the measurements.
Time Frame
Up to 24 months after completion of study treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed, cutaneous squamous cell carcinoma Patients must have disease that is deemed potentially resectable, at the time of the start of study, by the treating investigator. The decision to perform surgery on patients must be based on good clinical judgment. Eligible patients for surgical resection must have disease that, in the judgment of the surgeon, is deemed potentially resectable, resulting in free surgical margins Patients must have measurable disease Patients must have disease that is considered either: (1) high-risk localized CSCC, (2) locally recurrent CSCC, or (3) regionally advanced CSCC. The criteria specific to each of these populations is listed below For patients with high-risk localized CSCC, at least two of the following clinical or pathologic high-risk features must be present to be eligible: Clinical risk factors Any tumor size > 2.0 cm in diameter Tumors > 1.0 cm in high risk locations, including "mask areas" (central face, eyelids, eyebrow, nose, lips [cutaneous], periorbital, chin, mandible, preauricular and postauricular skin/sulci, genitalia, hands, feet, cheek, forehead, scalp, neck and pretibial) Any rapidly growing and/or symptomatic tumor Pathologic risk factors Poorly differentiated histology Depth > 6 mm in thickness Acantholytic / adenoid, adenosquamous, desmoplastic, or metaplastic / carcinosarcomatous histologic subtypes Invasion beyond subcutaneous fat Perineural, lymphatic, or vascular involvement Patients with locally recurrent CSCC, that failed prior surgery, radiation or systemic therapy, are eligible, as long as they have measurable disease and are deemed potentially resectable by the treating investigator Patients with regionally advanced CSCC, including in-transit, cutaneous, subcutaneous or lymph node metastases are eligible, as long as they have measurable disease and are deemed potentially resectable by the treating investigator Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Absolute neutrophil count >= 1,000 /mcL Absolute lymphocyte count >= 500 / mcL Hemoglobin >= 8.0 g/dL Platelets >= 75,000/mcl Total bilirubin =< 1.5 x institutional upper limit of normal Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SPGT]) =< 3 x institutional upper limit of normal Creatinine =< 1.8 mg/dl Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) Ability to understand and the willingness to sign a written informed consent and comply with surgical resection at end of study and other study-related procedures Exclusion Criteria: Metastatic disease that is unresectable. Patients with visceral metastases are not eligible. Regionally advanced disease, including in-transit, cutaneous, subcutaneous, or nodal metastases are allowed, if deemed potentially resectable by the investigator Prior treatment with cemiplimab or any other agent that blocks the PD-1 or PD-L1 pathway Prior treatment with other immune modulating agents within fewer than 4 weeks, prior to the first dose of cemiplimab. Examples of immune modulating agents include blockers of CTLA-4, 4-1BB, OX-40, therapeutic vaccines, or cytokine therapies Patients must not be receiving other concomitant biologic therapy, hormonal therapy, chemotherapy, other anti-cancer therapy or any other investigational agents while on this protocol Radiation therapy, non-cytotoxic agents or investigational agents in the 4 weeks prior to registration Immunosuppressive systemic corticosteroids equivalent to prednisone 10 mg or greater in the 14 days prior to the first dose of cemiplimab Any major surgery within 14 days prior to the first dose of cemiplimab. Patients must have recovered from any major complications before registration Active autoimmune disease requiring systemic treatment in the past 2 years (i.e. use of disease modifying agents or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment History of other prior malignancy in the last five years, with the exception of: adequately treated non-melanoma skin cancers (including multiple primary skin cancers), adequately treated in situ cancer, and other local tumors considered cured by local treatment (including melanoma) History of allergic reactions attributed to compounds of similar chemical or biologic composition to cemiplimab or any other PD-1 or PD-L1 inhibitor Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness / social situations that would limit compliance with study requirements Positive pregnancy test, active pregnancy or nursing / breast-feeding, due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants History solid organ or bone marrow transplantation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Charlean Ketchens, RN
Phone
323-865-3035
Email
Charlean.Ketchens@med.usc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gino K In, MD
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
Los Angeles County-USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charlean Ketchens
Phone
323-865-3035
Email
Charlean.Ketchens@med.usc.edu
First Name & Middle Initial & Last Name & Degree
Gino K. In, MD
Facility Name
USC / Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charlean Ketchens
Phone
323-865-3035
Email
Charlean.Ketchens@med.usc.edu
First Name & Middle Initial & Last Name & Degree
Gino K. In, MD
Facility Name
Hoag Memorial Hospital
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cristina de Leon
Phone
949-764-5543
Email
cristina.deleon@hoag.org
First Name & Middle Initial & Last Name & Degree
Jacob S. Thomas, MD
Facility Name
Northwestern University Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kavita Shah
Phone
312-695-2142
Email
kavita.shah@med.usc.edu
First Name & Middle Initial & Last Name & Degree
Sunandana Chandra, MD

12. IPD Sharing Statement

Learn more about this trial

A PD-1 Checkpoint Inhibitor (Cemiplimab) for High-Risk Localized, Locally Recurrent, or Regionally Advanced Skin Cancer

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