Clinical Trials /

Cetuximab in Head and Neck Cancer Patients

NCT03769311

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Cetuximab in Head and Neck Cancer Patients
  • Official Title: A Window of Opportunity Trial of Cetuximab in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC)

Clinical Trial IDs

  • ORG STUDY ID: UW18098
  • SECONDARY ID: P30CA014520
  • SECONDARY ID: P50DE026787
  • SECONDARY ID: NCI-2018-02990
  • SECONDARY ID: 2018-1232
  • NCT ID: NCT03769311

Conditions

  • Head and Neck Cancer
  • Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
CetuximabCTX, ErbituxPre-Operative Cetuximab Therapy

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Pre-Operative Cetuximab TherapyExperimentalTwo 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.
  • Cetuximab

Eligibility 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)

               -  Patients 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.

               -  Patients 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:

               -  Patients 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 patients 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.

        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.

          -  Prior malignancy except for the following:

               -  adequately treated basal cell or squamous cell skin cancer

               -  in situ cervical cancer

               -  adequately treated Stage I or II cancer from which the patient currently has no
                  evidence of disease

               -  Synchronous squamous cell carcinomas of the head/neck that are appropriate for
                  surgical resection as part of the clinical care

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in Tumor Size
Time Frame:up to 42 days
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Rate of Hospital Re-admission for CTX-related Complications
Time Frame:up to 42 days from on study
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Wisconsin, Madison

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