ERBITUX® Followed by Adjuvant Treatment With Chemoradiation and ERBITUX® for Locally Advanced Head and Neck Squamous Cell Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01218048
Recruitment Status : Active, not recruiting
First Posted : October 8, 2010
Last Update Posted : September 7, 2017
Bristol-Myers Squibb
Information provided by (Responsible Party):
Robert Ferris, University of Pittsburgh

Brief Summary:
There are currently no useful tests to identify patients who will respond to cetuximab therapy, notably because EGFR levels do not correlate with the clinical responses observed. Thus, the investigators are investigating the role of cellular immunity and immune escape mechanisms to explain the differential clinical response to cetuximab.

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of the Head and Neck Drug: Cetuximab Procedure: Surgery Radiation: Post-surgical radiation Drug: Cisplatin or carboplatin Phase 2

Detailed Description:
This prospective phase II clinical trial of preoperative, single-agent cetuximab treated patients is being conducted in order to obtain specimens before and after 4 weeks of cetuximab for immune biomarker studies. Stage III/IV HNC patients will be treated with definitive surgical resection and observed for disease recurrence. Cetuximab will be administered for a 3-4 week preoperative period to study biomarker modulation in correlation clinical response by CT scan and tumor apoptosis/proliferation after tumor excision, immediately after neoadjuvant cetuximab but before surgery. We will biopsy the skin/acneiform rash in all patients to correlate rash with biomarker modulation and clinical response. Cetuximab may also be given in the adjuvant setting. A primary scientific hypothesis will be tested: does short term pre-operative exposure to cetuximab modulate blood immune biomarkers and is immune modulation associated with anti-tumor effect? Forty (n=40) patients with complete specimens (tumor, peripheral blood mononuclear cells (PBMC) and serum) are necessary to enable adequate statistical power to be reached using paired specimens. A secondary set of hypotheses will evaluate the association between pre-operative biomarker levels and modulation with disease recurrence. The proposed trial will accrue stage II, III or IV surgical candidates without distant metastasis.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Neoadjuvant Immune Biomarker Modulation With Cetuximab Followed by Adjuvant Therapy With Concurrent Chemoradiotherapy or Radiotherapy With or Without Cetuximab for Locally Advanced Head and Neck Squamous Cell Carcinoma
Study Start Date : February 2011
Estimated Primary Completion Date : September 2017
Estimated Study Completion Date : October 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Neo-Adjuvant Cetuximab

Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation + Cisplatin (or Carboplatin)

NOTE: Based the results of surgery if the treating physician feels patient is not a candidate for chemotherapy, radiation can be given alone or with cetuximab.

Drug: Cetuximab
Pre-Surgery: IV, 400 mg/m2 day 1 then 250 mg/m2 alone days 8 and 15; Post-surgery: IV, 250 mg/m2 weekly concurrent with RT
Other Name: ERBITUX®
Procedure: Surgery
Surgery for tumor
Radiation: Post-surgical radiation
Radiation (2 Gy/d) to min of 60 Gy + max of 66 Gy post-surgery
Drug: Cisplatin or carboplatin
Cisplatin 30 mg/m2 or carboplatin AUC 1.5-2/week weekly, Concurrent with radiotherapy

Primary Outcome Measures :
  1. To determine the extent to which immune biomarkers are modulated in peripheral blood and HNC tumors by preoperative treatment with 4 consecutive weeks of single-agent cetuximab [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. To assess if neoadjuvant modulation of immune and signaling (EGFR pathway blockade) biomarkers can predict antitumor response to adjuvant cetuximab therapy and clinical outcome. [ Time Frame: 2 years ]
  2. To correlate biomarkers with the 2-year progression free survival and disease recurrence of HNC patients treated with surgery, postoperative chemoradiation and adjuvant cetuximab. [ Time Frame: 3 years ]
  3. To determine time to progression and overall survival. [ Time Frame: 3 years ]

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Histologically or cytologically confirmed, previously untreated HNC. Clinical stage III or IVA disease without distant metastases as determined by CT, and as defined by the American Joint Committee on Cancer Staging System, Sixth edition (See Appendix I).
  • Primary tumors of the oral cavity, oropharynx, hypopharynx, or larynx will be included. Primary tumors of the sinuses, paranasal sinuses, or nasopharynx, or unknown primary tumors are NOT allowed.
  • Macroscopic complete resection of the primary tumor must be planned.
  • Age greater than or equal to 18 years.
  • ECOG performance status 0-1.
  • Adequate hematologic, renal and hepatic function, as defined by:

    • Absolute neutrophil count (ANC) greater than or equal to 1,500/ul, platelets greater than or equal to 100,000/ul.
    • Creatinine clearance > 40
    • Bilirubin less than or equal to 1.5 x ULN, AST or ALT less than or equal to 2.5 x ULN.
  • Have signed written informed consent.

Exclusion Criteria:

  • Subjects who fail to meet the above criteria.
  • Prior severe infusion reaction to a monoclonal antibody.
  • Pregnancy or breastfeeding. Women of childbearing potential (WOCBP) must practice acceptable methods of birth control to prevent pregnancy. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.
  • All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation. The Investigator must immediately notify BMS in the event of a confirmed pregnancy in a patient participating in the study.
  • Subjects with an ECOG performance status of 2 or worse.
  • Evidence of distant metastasis.
  • Any other malignancy active within 5 years except for non-melanoma skin cancer or carcinoma in situ of the cervix, DCIS or LCIS of the breast.
  • Prior history of HNC.
  • Prior therapy targeting the EGFR pathway.
  • Any unresolved chronic toxicity greater than or equal to grade 2 from previous anticancer therapy (except alopecia), according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
  • Acute hepatitis, known HIV, or active uncontrolled infection.
  • History of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction within prior 6 months, untreated known coronary artery disease, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
  • Uncontrolled peptic or gastric ulcer disease, or gastrointestinal bleeding within prior 6 months.
  • Active alcohol abuse or other illness that carries a likelihood of inability to comply with study treatment and follow-up.
  • Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study 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 identifier (NCT number): NCT01218048

United States, Pennsylvania
UPCI - Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Robert Ferris
Bristol-Myers Squibb
Principal Investigator: Rober L Ferris, MD, PhD University of Pittsburgh Med Ctr (UPCI)

Responsible Party: Robert Ferris, MD, University of Pittsburgh Identifier: NCT01218048     History of Changes
Other Study ID Numbers: UPCI 08-013
First Posted: October 8, 2010    Key Record Dates
Last Update Posted: September 7, 2017
Last Verified: September 2017

Keywords provided by Robert Ferris, University of Pittsburgh:
Head and Neck
Locally Advanced Head and Neck Squamous Cell Carcinoma

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