Cetuximab in Head and Neck Cancer Patients

NCT03769311 | Completed Phase 2 Results DMC FDA Drug

• 7 other identifiers: UW18098P50DE026787NCI-2018-029902018-1232A534260SMPH/MEDICINE/HEM-ONCProtocol Version 6/26/2020
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is for participants with head and neck squamous cell carcinoma who are scheduled to have their tumor surgically removed. The study involves obtaining baseline tissue from a clinical biopsy or research biopsy and measurement of circulating tumor cells before surgery to determine whether AXL protein expression pre-treatment correlates to clinical outcomes (change in tumor size) after two doses of cetuximab. The importance of this study is to describe if AXL expression can be used as a biomarker to predict clinical response to cetuximab (CTX) treatment.

Conditions

Head and Neck Cancer; Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Change in Tumor Size

  The tumor size (via clinical measurements) will be measured from the time of diagnosis (pre-CTX) to after treatment with 2 doses of cetuximab and within 48 hours prior to surgery (post-CTX). Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Committee criteria will be used to define clinical response (partial response, progressive disease, or stable disease) prior to surgery.

  up to 42 days

• Objective Tumor Response Rate - AXL Expression

  The levels of AXL expression (low vs high, ranges from 0-4+ with 4+ meaning intense staining in the majority of cancer cells and 0 meaning no staining at all) at the time of diagnosis (pre-CTX) will measured and compared to change in the tumor size as reported in Primary Outcome Measure 1.

  up to 42 days

Secondary Outcomes (1)

• Number of Hospital Re-admission for CTX-related Complications

  within 28 days after surgery

Other Outcomes (2)

• Change in Ki67 From Pre- vs Post-CTX Treated Tumors

  up to 30 months

• Correlation of Measures of Putative Markers of CTX Sensitivity

  up to 30 months

Study Arms (1)

Pre-Operative Cetuximab Therapy

EXPERIMENTAL

Two weekly doses of pre-operative cetuximab during the interval between diagnostic HNSCC biopsy and surgery (\~14 days), ensuring that no delay in standard of care (SOC) will occur. For dose #1, participants will receive cetuximab 400 mg/m2 via intravenous infusion over 2 hours (maximum infusion rate 10 mg/min) as per the standard of care loading regimen for cetuximab monotherapy. For dose #2, participants will receive cetuximab 250 mg/m2 via intravenous infusion over 1 hour (maximum infusion rate 10 mg/min) as per the standard of care dosing regimen for cetuximab monotherapy.

Drug: Cetuximab

Interventions

Cetuximab DRUG

Monoclonal antibody against epidermal growth factor receptor (EGFR)

Also known as: CTX, Erbitux

Pre-Operative Cetuximab Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent: participants must be informed of the investigational nature of the study and must be able to sign a written informed consent.
• Participants must have suspected or known clinical presentation of head and neck squamous cell carcinoma or a recurrence of head and neck squamous cell carcinoma after initial therapy. For newly suspected head and neck cancer, the procedure will obtain tissue for both standard of care biopsy and additional tissue for research.
• Participants must have sufficient tumor volume (approximately 10 cc) to accommodate at minimum 2-3 core samples for the research biopsy. This will be approximated based on clinical evidence, such as physician visualization or palpitation.
• Participants are required to consent to the TSB Biobank protocol (2016-0934) as part of this study.
• Surgical management must be the chosen modality for management of the head and neck squamous cell cancer.
• Other therapeutic modalities may follow, but surgery must be the choice for first therapy rendered.
• Participants must have a biopsy proven, squamous cell carcinoma of the head and neck, excluding advanced cutaneous head and neck squamous cell carcinoma.
• ECOG performance status £ 1
• Women of childbearing potential (WOCP) must not be pregnant (confirmed by a negative urine/serum pregnancy test within 7 days of cetuximab treatment). In addition, a medically acceptable method of birth control must be used such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence during the study participation and for 6 months after last dose of study drug. Women who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are not considered to be WOCP.
• Men who are not surgically or medically sterile must agree to use an acceptable method of contraception. Male participants with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant must agree to use condoms during the study and for 6 months post study drug. Total abstinence for the same study period is an acceptable alternative.
• Participants with other concomitant malignancies are allowed to participate on the clinical trial as long as the surgical resection of the head and neck squamous cell carcinoma is clinically indicated.
• Participants with metastatic disease are allowed to participate on the clinical as long as the surgical resection of the head and neck squamous cell carcinoma is clinically indicated.

You may not qualify if:

• Diagnosis of nasopharyngeal carcinoma, advanced cutaneous squamous cell carcinoma of the head \& neck, and salivary gland tumors
• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
• Prior chemotherapy, radiotherapy, or major surgery within 8 weeks of study enrollment or those who have not recovered (to grade ≤ 1 or baseline) from clinically significant adverse events due to agents administered more than 8 weeks earlier (alopecia and fatigue excluded). Clinical significance to be determined by the study investigator
• Prior cetuximab therapy is allowed so long as administered ³ 8 weeks ago.
• History of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab
• Pregnancy, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 6 months after the last dose of trial treatment
• Ongoing or active infection, including active tuberculosis or known infection with the human immunodeficiency virus (HIV)
• Ongoing treatment with other investigational agents.
• Any of the following cardiac conditions:
• uncontrolled or poorly-controlled arrhythmia or uncontrolled cardiac insufficiency uncontrolled or poorly-controlled hypertension (\>180 mmHg systolic or \> 130 mmHg diastolic)
• Any of the following conditions:
• serious or non-healing wound, ulcer, or bone fracture
• history of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 28 days of study enrollment
• history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study enrollment
• history of myocardial infarction, ventricular arrhythmia, stable/unstable angina, symptomatic congestive heart failure, coronary/peripheral artery bypass graft or stenting or other significant cardiac disease within 6 months prior to study enrollment

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator
• American Cancer Society, Inc.: collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Justine Bruce, MD
• Organization: University of Wisconsin Carbone Cancer Center

jybruce@medicine.wisc.edu

608-262-4961

Study Officials

• Justine Bruce

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single site, open label, window of opportunity study

Study Record Dates

• First Submitted: November 28, 2018
• First Posted: December 7, 2018
• Study Start: April 17, 2019
• Primary Completion: March 15, 2022
• Study Completion: March 15, 2022
• Last Updated: May 24, 2023
• Results First Posted: May 24, 2023

Record last verified: 2023-05

Locations

US (1)