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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by University of Pittsburgh
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01218048
First received: October 7, 2010
Last updated: December 10, 2012
Last verified: December 2012

October 7, 2010
December 10, 2012
February 2011
January 2014   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01218048 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • To determine time to progression and overall survival. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
ERBITUX® Followed by Adjuvant Treatment With Chemoradiation and ERBITUX® for Locally Advanced Head and Neck Squamous Cell Carcinoma
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

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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Squamous Cell Carcinoma of the Head and Neck
  • 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
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.

Interventions:
  • Drug: Cetuximab
  • Procedure: Surgery
  • Radiation: Post-surgical radiation
  • Drug: Cisplatin or carboplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
January 2015
January 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: Brittni Prosdocimo, RN 412-623-4126 bittnerb@upmc.edu
Contact: Robert Ferris, MD 412-623-0327 ferrisrl@upmc.edu
United States
 
NCT01218048
UPCI 08-013
Yes
University of Pittsburgh
University of Pittsburgh
Bristol-Myers Squibb
Principal Investigator: Rober L Ferris, MD, PhD University of Pittsburgh Med Ctr (UPCI)
University of Pittsburgh
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP