Clinical Trials /

Cemiplimab Before and After Surgery for the Treatment of High Risk Cutaneous Squamous Cell Cancer

NCT04428671

Description:

This phase I trial studies how well cemiplimab before and after surgery works in treating patients with high risk cutaneous squamous cell cancer. 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. Giving cemiplimab before surgery may improve risk of the cancer returning in patients with high risk cutaneous squamous cell cancer.

Related Conditions:
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Cemiplimab Before and After Surgery for the Treatment of High Risk Cutaneous Squamous Cell Cancer
  • Official Title: Pilot Study of Neoadjuvant/Adjuvant Cemiplimab for High Risk Cutaneous Squamous Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: IRB00115160
  • SECONDARY ID: NCI-2019-07373
  • SECONDARY ID: IRB00115160
  • SECONDARY ID: Winship4851-19
  • SECONDARY ID: P30CA138292
  • NCT ID: NCT04428671

Conditions

  • Metastatic Skin Squamous Cell Carcinoma
  • Recurrent Skin Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
CemiplimabCemiplimab RWLC, Cemiplimab-rwlc, Libtayo, REGN2810Treatment (cemiplimab)

Purpose

This phase I trial studies how well cemiplimab before and after surgery works in treating patients with high risk cutaneous squamous cell cancer. 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. Giving cemiplimab before surgery may improve risk of the cancer returning in patients with high risk cutaneous squamous cell cancer.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To establish the pathologic response rate of neoadjuvant cemiplimab in cutaneous squamous
      cell carcinoma (cSCC).

      SECONDARY OBJECTIVES:

      I. To document the local recurrence rate of high-risk cSCC treated with adjuvant cemiplimab.

      II. To document the systemic recurrence rate of high-risk cSCC treated with adjuvant
      cemiplimab.

      III. To document the 6-month, 12-month, 2-year overall survival (OS), recurrence-free
      survival (RFS) for patients with high risk cSCC.

      TERTIARY/EXPLORATORY OBJECTIVE:

      I. To evaluate the immune profile of fresh tumor tissue, blood in patients with cSCC treated
      with cemiplimab.

      OUTLINE:

      NEOADJUVANT PHASE: Prior to standard of care surgery, patients receive cemiplimab
      intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 3
      cycles in the absence of disease progression or unacceptable toxicity.

      ADJUVANT PHASE: Within 2-6 weeks after completion of standard of care radiation therapy (or
      surgery if no radiation therapy), patients receive cemiplimab IV over 30 minutes on day 1.
      Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up every 12 weeks for 2 years,
      every 6 months for the next 3 years, and then annually for up to 10 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (cemiplimab)ExperimentalNEOADJUVANT PHASE: Prior to standard of care surgery, patients receive cemiplimab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. ADJUVANT PHASE: Within 2-6 weeks after standard of care radiation therapy (or surgery if no radiation therapy), patients receive cemiplimab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.
  • Cemiplimab

Eligibility Criteria

        Inclusion Criteria:

          -  Patient must have a known diagnosis of high risk cSCC defined by the following
             criteria:

               -  Nodal disease with extracapsular extension (ECE) and at least one node >= 20 mm
                  on the surgical pathology report

               -  In-transit metastases (ITM) defined as skin or subcutaneous metastases that are >
                  2 cm from the primary lesion but are not beyond the regional nodal basin

               -  T4 lesion for head and neck CSCC

               -  Perineural invasion (PNI), defined as clinical and/or radiologic involvement of
                  named nerves

               -  Recurrent CSCC, defined as CSCC that arises within the area of the previously
                  resected tumor, plus at least one of the following additional features:

                    -  >= N2b disease associated with the recurrent lesion

                    -  Nominal >= T3 (recurrent lesion >= 4 cm in diameter or minor bone erosion or
                       deep invasion > 6 mm measured from the granular layer of normal adjacent
                       epithelium)

                    -  Poorly differentiated histology and >= 20 mm diameter of recurrent lesion.
                       The recurrent lesion must be documented to be within the area of the
                       previously resected CSCC by radial measurement of the greatest radius of the
                       final defect, measured from the estimated center of the original surgical
                       wound

          -  Cancer confirmed to be surgically resectable, with surgery evaluation with planned
             prior to resection

          -  No prior systemic immunotherapy, no prior anti-PD1 therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 1

          -  Hemoglobin >= 9.0 g/dl (within 28 days of cycle 1 day 1)

          -  Absolute neutrophil count (ANC) >= 1,500/mcL (within 28 days of cycle 1 day 1)

          -  Platelets >= 100,000/mcL (within 28 days of cycle 1 day 1)

          -  Total bilirubin =<1.5 institutional upper limit of normal (ULN) (within 28 days of
             cycle 1 day 1)

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 institutional
             upper limit of normal (ULN) (within 28 days of cycle 1 day 1)

          -  Albumin >= 3.0 g/dL (within 28 days of cycle 1 day 1)

          -  Serum creatinine =< 1.5 x ULN (or calculated creatinine clearance of >= 50 mL/min
             using Cockcroft-Gault formula) (within 28 days of cycle 1 day 1)

          -  International normalized ratio (INR) =< 1.5 (within 28 days of cycle 1 day 1)

               -  Anticoagulation is allowed only with low molecular weight heparin (LMWH). Patient
                  receiving LMW heparin on stable therapeutic dose for more than 2 weeks or with
                  factor Xa level < 1.1U/mL are allowed on the trial

          -  Clinically significant toxic effect(s) of the most recent prior anti-cancer therapy
             must be grade 1 or resolved (except alopecia and sensory neuropathy); patients with
             grade 2 adrenal insufficiency related to prior anti-cancer therapy (defined as
             requiring medical intervention, such as concomitant steroids) or grade 2
             hypothyroidism (defined as requiring hormone replacement therapy) may be enrolled
             provided that clinical symptoms are adequately controlled and the daily dose is 10 mg
             or less of prednisone or equivalent. If the patient received major surgery or
             radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or
             complications from the intervention

          -  Patients with a prior or concurrent malignancy whose natural history or treatment does
             not have the potential to interfere with the safety or efficacy assessment of the
             investigational regimen are eligible for this trial

          -  The effects of cemiplimab on the developing human fetus are unknown. For this reason
             female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy
             test prior to starting therapy

          -  FCBP and men must agree to use adequate contraception (at least one highly effective
             method and one additional method of birth control at the same time or complete
             abstinence) prior to study entry, for the duration of study participation and for at
             least 6 months following study drug discontinuation. Should a woman become pregnant or
             suspect she is pregnant while she or her partner is participating in this study, she
             should inform her treating physician immediately. A female of childbearing potential
             (FCBP) is a sexually mature woman who: has not undergone a hysterectomy or bilateral
             oophorectomy or has not been naturally postmenopausal for at least 12 consecutive
             months (if age >= 55 years); if the female subject is < 55 years and she has been
             naturally postmenopausal for >= 1 year her reproductive status has to be verified by
             additional lab tests (< 20 estradiol OR estradiol < 40 with follicle stimulating
             hormone [FSH] > 40 in women not on estrogen replacement therapy)

          -  Patients must agree not to donate blood, sperm/ova while taking protocol therapy and
             for at least 6 months after stopping treatment

          -  Willingness and ability of the subject to comply with scheduled visits, drug
             administration plan, protocol-specified laboratory tests, other study procedures, and
             study restrictions

          -  Evidence of a personally signed informed consent indicating that the subject is aware
             of the neoplastic nature of the disease and has been informed of the procedures to be
             followed, the experimental nature of the therapy, alternatives, potential risks and
             discomforts, potential benefits, and other pertinent aspects of study participation

        Exclusion Criteria:

          -  Determined not to be a surgical candidate due to medical co-morbidities or extent of
             disease

          -  Treatment with chronic immunosuppressants (e.g., cyclosporine following
             transplantation)

          -  Prior organ allograft or allogeneic bone marrow transplantation

          -  Subjects with active or history of immune mediated pneumonitis, colitis, hepatitis,
             nephritis, or skin reactions as these patients may be at increased risk for developing
             immune therapy-induced exacerbation or recurrence of their immune mediated disease,
             potentially delaying surgery

          -  Subjects with a condition requiring systemic treatment with either corticosteroids (>
             10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
             days of study drug administration. Inhaled or topical steroids and adrenal replacement
             doses > 10 mg daily prednisone equivalents are permitted in the absence of active
             autoimmune disease

          -  Women who are pregnant or lactating

          -  Uncontrolled intercurrent illness including, but not limited to, human
             immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral
             therapy, ongoing or active infection, symptomatic congestive heart failure (New York
             Heart Association [NYHA] class III or IV), unstable angina pectoris, ventricular
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Other medications, or severe acute/chronic medical or psychiatric condition, or
             laboratory abnormality that may increase the risk associated with study participation
             or study drug administration, or may interfere with the interpretation of study
             results, and in the judgment of the investigator would make the subject inappropriate
             for entry into this study

          -  Clinical evidence of bleeding diathesis or coagulopathy

          -  Subjects with a history of severe allergic reactions

          -  Patients with prior malignancies, are eligible if they have been disease free for > 3
             years

          -  Patients with prior low-risk non-melanoma skin cancers and in situ carcinomas are
             eligible provided there was complete removal

          -  Use of other investigational drugs (drugs not marked for any indication) within 28
             days or at least 5 half-lives (whichever is longer) before study drug administration

          -  History of severe hypersensitivity reactions to other monoclonal antibodies

          -  Non-oncology vaccines within 28 days prior to starting treatment

          -  Prisoners and subjects who are compulsory detained
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic response rate
Time Frame:From screening up to 10 years post-treatment
Safety Issue:
Description:Defined as the number of complete and partial responses divided by the total number of patients, as assessed by pathology. Pathological complete response (pCR) (no viable tumor) or pathological partial response (pPR) (less than 50% viable tumor) as well as near pCR (less than 10% viable tumor) in the tumor bed will be documented by pathology from the resection specimen. Pathologic response rate will be summarized using frequency and percentage, and a 95% exact confidence interval will be reported using the Clopper-Pearson method.

Secondary Outcome Measures

Measure:Time to local recurrence
Time Frame:From screening to local recurrence, death, or last known follow-up, assessed up to 10 years post-treatment
Safety Issue:
Description:Local recurrence-free survival will be estimated using the Kaplan-Meier method.
Measure:Time to systemic recurrence
Time Frame:From screening to systemic recurrence, death, or last known follow-up, assessed up to 10 years post-treatment
Safety Issue:
Description:Systemic recurrence-free survival will be estimated using the Kaplan-Meier method.
Measure:Overall survival (OS)
Time Frame:From screening to death from any cause or last known follow-up, assessed up to 2 years post-treatment
Safety Issue:
Description:OS will be estimated using the Kaplan-Meier method. 6-month, 12-month, and 24-month OS estimates will be reported along with 95% confidence intervals.
Measure:Recurrence-free survival (RFS)
Time Frame:From screening to recurrence, death, or last known follow-up, assessed up to 2 years post-treatment
Safety Issue:
Description:RFS will be estimated using the Kaplan-Meier method. 6-month, 12-month, and 24-month RFS estimates will be reported along with 95% confidence intervals.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Emory University

Last Updated

June 29, 2020