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
  Purpose

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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 40
Study Start Date: February 2011
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01218048

Contacts
Contact: Brittni Prosdocimo, RN 412-623-4126 bittnerb@upmc.edu
Contact: Robert Ferris, MD 412-623-0327 ferrisrl@upmc.edu

Locations
United States, Pennsylvania
UPCI - Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Robert Ferris, MD    412-623-0327    ferrisrl@upmc.edu   
Sponsors and Collaborators
University of Pittsburgh
Bristol-Myers Squibb
Investigators
Principal Investigator: Rober L Ferris, MD, PhD University of Pittsburgh Med Ctr (UPCI)
  More Information

No publications provided

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01218048     History of Changes
Other Study ID Numbers: UPCI 08-013
Study First Received: October 7, 2010
Last Updated: December 10, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Carcinoma
Head and Neck
Cetuximab
Locally Advanced Head and Neck Squamous Cell Carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cetuximab
Cisplatin
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 28, 2014