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Cetuximab in Head and Neck Cancer Patients

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ClinicalTrials.gov Identifier: NCT03769311
Recruitment Status : Recruiting
First Posted : December 7, 2018
Last Update Posted : August 13, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Institute of Dental and Craniofacial Research (NIDCR)
Information provided by (Responsible Party):
University of Wisconsin, Madison

Brief Summary:
This clinical trial is for patients 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.

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Squamous Cell Carcinoma Drug: Cetuximab Phase 2

Detailed Description:

This is a window of opportunity trial evaluating the hypothesis that AXL levels correlate with clinical response to cetuximab in head and neck patients. Patients with head and neck squamous cell carcinoma who are scheduled to undergo surgical resection of their tumor and are candidates for cetuximab chemotherapy are eligible to participate.

Primary:

1. To test the hypothesis that low AXL correlates with clinical response to cetuximab in head and neck cancer patients

Secondary:

1. To further describe the safety of pre-operative administration of cetuximab

Correlative:

  1. To correlate AXL expression with change in Ki67 following cetuximab in Head and Neck Cancer (HNC) patients
  2. To examine other putative markers of cetuximab sensitivity such as HER3 and change in circulating tumor cells
  3. To establish the first panel of patient-derived xenografts from patients with known sensitivity or resistance to cetuximab

Following informed consent, tumor tissue from the research biopsy and a blood draw for circulating tumor cells will be obtained. The patient will then receive two weekly doses of pre-operative cetuximab during the interval between diagnostic biopsy and surgery (~14 days), ensuring that no delay in standard of care (SOC) will occur.

For dose #1, patients 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, patients 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.

At the time of surgery, another blood draw will be obtained for analysis of circulating tumor cells, and a portion of the resected tumor will be obtained for study analysis.

Correlative studies will include the measurement of proteins hypothesized to be involved in cetuximab resistance such as AXL, Ki67, EGFR, and HER3 expression from both the biopsy and the surgical specimen. Blood will be analyzed for correlative analysis of circulating tumor cells. Tissue from the research biopsy will be utilized for patient-derived xenograft (PDX) development.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Single site, open label, window of opportunity study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Window of Opportunity Trial of Cetuximab in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC)
Actual Study Start Date : May 8, 2019
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

Arm Intervention/treatment
Experimental: Pre-Operative Cetuximab Therapy
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, patients 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, patients 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
Monoclonal antibody against epidermal growth factor receptor (EGFR)
Other Names:
  • CTX
  • Erbitux




Primary Outcome Measures :
  1. Change in Tumor Size [ Time Frame: up to 42 days ]
    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 prior to surgery.

  2. Objective Tumor Response Rate - AXL expression [ Time Frame: up to 42 days ]
    The levels of AXL expression (low vs high) at the time of diagnosis (pre-CTX) will measured and compared to change in the tumor size as reported in Primary Outcome Measure 1. The relationship between AXL expression as a continuous variable with clinical response will be analyzed using the Wilcoxon rank sum test.


Secondary Outcome Measures :
  1. Rate of Hospital Re-admission for CTX-related Complications [ Time Frame: up to 42 days from on study ]
    Hospital re-admission for wound healing, surgical complications, or infection that occur within 28 days after surgery will be categorized as definitely related, probably related, possibility related, unlikely related, or unrelated to cetuximab administration and will be reported as a proportion including an exact 95% confidence interval.


Other Outcome Measures:
  1. Change in Ki67 from Pre- vs Post-CTX Treated Tumors [ Time Frame: up to 30 months ]
    Summary statistics of the change in Ki67 (ΔKi67), as established by the surgical specimen, will be reported for the response to cetuximab endpoint.

  2. Correlation of Measures of Putative Markers of CTX Sensitivity [ Time Frame: up to 30 months ]
    Markers include: protein, RNA, circulating tumor cells with CTX response, measured by Ki67. Correlation between ΔKi67 and putative biomarkers will be analyzed as a continuous variable and will be tested using Pearson's correlation coefficient. Correlation between two biomarkers such as AXL and HER3 expression as continuous variables will be investigated using Pearson's correlation coefficient. Summary statistics will be used to report circulating tumor cells at each time point and the changes between time points. The association of change in circulating tumor cells with ΔKi67 (early response) will be explored graphically and with Pearson's correlation coefficient.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Informed consent: patients must be informed of the investigational nature of the study and must be able to sign a written informed consent.

  • Inclusion criteria for research biopsy (screen)

    • 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.
  • Inclusion criteria for cetuximab treatment:

    • 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.

Exclusion Criteria:

  • 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.
  • Evidence of distant metastatic disease
  • 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
    • history of arterial or venous thrombosis/thromboembolic event, including pulmonary embolism within 6 months of study enrollment
    • any condition requiring the use of immunosuppression, excluding rheumatologic conditions treated with stable doses of corticosteroids
    • Use of herbal supplements (St. John's Wort, gingko biloba, etc.) within one week of cetuximab treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03769311


Contacts
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Contact: Cancer Connect 800-622-8922 cancerconnect@uwcarbone.wisc.edu

Locations
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United States, Wisconsin
University of Wisconsin Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53792
Contact: Diana Trask    608-263-9528    trask@humonc.wisc.edu   
Principal Investigator: Justine Bruce, MD         
Sponsors and Collaborators
University of Wisconsin, Madison
National Cancer Institute (NCI)
National Institute of Dental and Craniofacial Research (NIDCR)
Investigators
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Principal Investigator: Justine Bruce University of Wisconsin, Madison

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Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT03769311     History of Changes
Other Study ID Numbers: UW18098
P30CA014520 ( U.S. NIH Grant/Contract )
P50DE026787 ( U.S. NIH Grant/Contract )
NCI-2018-02990 ( Other Identifier: NCI Trial ID )
2018-1232 ( Other Identifier: Institutional Review Board )
First Posted: December 7, 2018    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents