Clinical Trials /

Cetuximab Before Surgery in Treating Patients With Aggressive Locally Advanced Skin Cancer

NCT02324608

Description:

This pilot clinical trial studies the side effects and how well cetuximab before surgery works in treating patients with skin cancer that forms, grows, and spreads quickly and has spread from where it started to nearby tissue or lymph nodes. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways be targeting certain cells. Giving cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Related Conditions:
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Cetuximab Before Surgery in Treating Patients With Aggressive Locally Advanced Skin Cancer
  • Official Title: A Pilot Study of Neoadjuvant Cetuximab in Advanced Squamous Cell Carcinomas of Skin (SCCS)

Clinical Trial IDs

  • ORG STUDY ID: 091303
  • SECONDARY ID: NCI-2014-02027
  • SECONDARY ID: 091303
  • SECONDARY ID: P30CA072720
  • NCT ID: NCT02324608

Conditions

  • Recurrent Skin Cancer
  • Squamous Cell Carcinoma of the Skin

Interventions

DrugSynonymsArms
cetuximabC225, C225 monoclonal antibody, IMC-C225, MOAB C225, monoclonal antibody C225Treatment (cetuximab)

Purpose

This pilot clinical trial studies the side effects and how well cetuximab before surgery works in treating patients with skin cancer that forms, grows, and spreads quickly and has spread from where it started to nearby tissue or lymph nodes. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways be targeting certain cells. Giving cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the response rate of cetuximab by Response Evaluation Criteria in Solid Tumors
      (RECIST) criteria in patients with advanced squamous cell carcinoma of skin (SCCS).

      II. To assess whether neoadjuvant cetuximab given in this patient population is both safe and
      feasible.

      SECONDARY OBJECTIVES:

      I. To measure the progression free and overall survival of patients with advanced SCCS who
      receive neoadjuvant cetuximab.

      II. To determine the conversion to resectability of patients treated with neoadjuvant
      cetuximab and capture changes in reconstructive options rendered possible by neoadjuvant
      treatment.

      III. Analyze the relationship of known deoxyribonucleic acid (DNA) mutations in tumor per the
      FoundationOneTM genomic profile, and correlate to clinical endpoints such as clinical benefit
      and conversion to resectability to discover potential markers of response and/or resistance.

      IV. Measure the downstream activation of signaling pathways without a known driver, including
      the epidermal growth factor receptor (EGFR) pathway.

      V. Determine if tumor shrinkage with cetuximab is associated with increased apoptosis as
      evidenced by activated caspase-3, in pre- and post- treatment tumor tissues.

      VI. Determine whether cetuximab results in increased antibody-dependent cell cytotoxicity
      (ADCC) in post-, compared with pre-treatment tumor tissues.

      OUTLINE:

      Patients receive cetuximab intravenously (IV) over 60-120 minutes once weekly for 8 weeks.

      After completion of study treatment, patients are followed up every 3 months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (cetuximab)ExperimentalPatients receive cetuximab IV over 60-120 minutes once weekly for 8 weeks.
  • cetuximab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have untreated or relapsed SCCS that is considered to be aggressive and
             locally advanced by the following criteria: tumors 2 cm or more, tumors invading deep
             tissues such as muscle, cartilage or bone; tumors showing perineural invasion, and/or
             tumors metastatic to loco-regional lymph nodes; patients may have had prior surgical
             interventions or been treated with investigational agents with residual or recurrent
             disease

          -  Patients must give informed consent

          -  Patients must agree to pre- and post-treatment biopsies

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =<
             2

          -  Estimated life expectancy of at least 12 weeks

          -  Negative pregnancy test

        Exclusion Criteria:

          -  Second primary malignancy only if treatment would interfere with the patient's
             participation in this trial in the opinion of the treating physician; clear exceptions
             are 1) patient had a second primary malignancy but has been treated and disease free
             for at least 3 years, 2) in situ carcinoma (e.g. in situ carcinoma of the cervix) and,
             3) additional skin cancers that have been definitively treated by surgery and/or
             radiation; patients with chronic lymphocytic leukemia will be allowed if their blood
             counts are within acceptable hematologic parameters and if they are not currently
             requiring cytotoxic or biologic anticancer treatment (supportive treatment such as
             intravenous immunoglobulin [IVIG] is permitted)

          -  Patients with distant organ metastases will not be included in this study

          -  Serious concomitant systemic disorders (including active infections) that would
             compromise the safety of the patient or compromise the patient's ability to complete
             the study, at the discretion of the investigator

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to cetuximab or other agents used in the study

          -  Women who are pregnant; women of childbearing age must agree to undergo a pregnancy
             test prior to therapy and to use adequate contraception (hormonal or barrier method of
             birth control; abstinence) prior to study entry, for the duration of study
             participation and for 6 months after; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

          -  Serum calcium (ionized or adjusted for albumin) < 8 mg/dl (1.75 mmol/L) or > 12.5
             mg/dl (> 3.1 mmol/L) despite intervention to normalize levels

          -  Magnesium < 1.4 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention
             to normalize levels

          -  Potassium < 3.5 mmol/L or > 6 mmol/L despite intervention to normalize levels

          -  Prior radiation therapy is not an exclusion however, patient must have documented
             progression at the radiation site
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate of cetuximab by RECIST criteria
Time Frame:Up to 2 years
Safety Issue:
Description:A one-sided Binomial exact test will be used.

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:Up to 2 years
Safety Issue:
Description:The estimation of progression-free survival will be performed by the Kaplan-Meier product limit method. Descriptive statistics for all outcome measures will be provided. To evaluate the association between variables, either chi-square test (categorical vs. categorical) or two sample t-test (categorical vs. continuous) or correlation (continuous vs. continuous) will be used depending upon the types of variables in comparison.
Measure:Overall survival
Time Frame:Up to 2 years
Safety Issue:
Description:The estimation of overall survival will be performed by the Kaplan-Meier product limit method. Descriptive statistics for all outcome measures will be provided. To evaluate the association between variables, either chi-square test (categorical vs. categorical) or two sample t-test (categorical vs. continuous) or correlation (continuous vs. continuous) will be used depending upon the types of variables in comparison.
Measure:Downstream activation of signaling pathways without a known driver, including the EGFRpathway
Time Frame:Up to 2 years
Safety Issue:
Description:Measure the downstream activation of signaling pathways without a known driver, including the EGFRpathway
Measure:Potential markers of response and/or resistance to cetuximab therapy
Time Frame:Up to 2 years
Safety Issue:
Description:Analyze the relationship of known DNA mutations in tumor per the FoundationOneTM genomic profile, and correlate to clinical endpoints such as clinical benefit and conversion to resectability to discover potential markers of response and/or resistance to cetuximab therapy.

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Rutgers, The State University of New Jersey

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