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

A Pilot Study of Neoadjuvant Cetuximab in Advanced Squamous Cell Carcinomas of Skin (SCCS)

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.

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma of the Skin; Recurrent Skin Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Biological: cetuximab

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (cetuximab); Patients receive cetuximab IV over 60-120 minutes once weekly for 8 weeks.	Other: laboratory biomarker analysis; Correlative studies; Biological: cetuximab; Given IV; Other Names: C225; IMC-C225; C225 monoclonal antibody; MOAB C225; monoclonal antibody C225

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate of Cetuximab by RECIST Criteria	A one-sided Binomial exact test will be used.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	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.	Up to 2 years
Overall Survival	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.	Up to 2 years
Downstream Activation of Signaling Pathways Without a Known Driver, Including the EGFRpathway	Measure the downstream activation of signaling pathways without a known driver, including the EGFRpathway	Up to 2 years
Potential Markers of Response and/or Resistance to Cetuximab Therapy	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.	Up to 2 years

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI); Rutgers Cancer Institute of New Jersey
• Investigators: Principal Investigator: Adam Berger, MD, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2015
• Primary Completion (Actual): December 9, 2020
• Study Completion (Actual): May 30, 2023

Study Registration Dates

• First Submitted: October 28, 2014
• First Submitted That Met QC Criteria: December 18, 2014
• First Posted (Estimated): December 24, 2014

Study Record Updates

• Last Update Posted (Estimated): December 20, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Skin Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: 091303 (Rutgers Cancer Institute of New Jersey); P30CA072720 (U.S. NIH Grant/Contract); Pro20140000555 (Other Identifier: Rutgers Cancer Institute of New Jersey); NCI-2014-02027 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO