Preoperative Treatment With Cetuximab and/or IMC-A12 - Full Text View

Purpose

The goal of this clinical research study is to give cetuximab and/or IMC-A12 before surgery for squamous cell carcinoma of the head and neck, in order to learn if these study drugs may cause changes in biomarkers. Biomarkers are chemical "markers" in the blood and/or tissue that may be related to a reaction to study treatment.

The safety of the study treatments will also be studied.

Objectives:

1.1 Primary Objectives: The primary objective of this study is to assess the degree of modulation of phospho-AKT in Head and Neck Squamous Cell Carcinoma after a short, pre-operative course of treatment with cetuximab and/or IMC-A12.

1.2 Secondary Objectives:

The secondary objectives of this study are to assess:

Safety of cetuximab and/or IMC-A12 (particularly in the pre-operative setting),
Effects of IMC-A12 on glucose metabolism (with an emphasis on the pathophysiology of hyperglycemia).
Modulation of a panel of biomarkers in HNSCC after treatment with cetuximab and/or IMC-A12 and attempt correlation with clinical outcomes.
Objective response to, and histopathological changes after the short course of treatment.

Condition	Intervention	Phase
Head and Neck Squamous Cell Carcinoma	Drug: Cetuximab Drug: IMC-A12 Procedure: Surgical tumor resection	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Exploratory Study to Assess the Modulation of Biomarkers in Patients With Squamous Cell Carcinomas of the Head and Neck Randomized to Receive Preoperative Treatment With Cetuximab and/or IMC-A12, an Anti-insulin-like Growth Factor-1 Receptor Monoclonal Antibody

Resource links provided by NLM:

MedlinePlus related topics: Cancer Diabetes Medicines

Drug Information available for: Cetuximab

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Modulation of phospho-Akt (difference in IHC score between the surgical specimen and the baseline biopsy) [ Time Frame: Biopsy at baseline and surgery (surgery should be within 10 days of last treatment). ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	October 2011
Estimated Primary Completion Date:	October 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group 1: Cetuximab Cetuximab: 400 mg/m2 i.v. over 120 minutes on week 1, and 250 mg/m2 on week 2 and 3 i.v. over 60 minutes	Drug: Cetuximab First dose of 400 mg/m^2 by vein on Days 1 and 8 over 2 hours, second dose of 250 mg/m^2 on week 2 and 3 (if applicable) given over 1 hour. Other Names: C225 Erbitux IMC-C225 Procedure: Surgical tumor resection Surgical tumor resection on Day 10.
Experimental: Group 2: IMC-A12 IMC-A12: 6 mg/kg/week i.v. over 1 hour on weeks 1 and 2 and 3.	Drug: IMC-A12 6 mg/kg/week by vein on Days 1 and 8 over 1 hour on weeks 1 and 2 and 3 (if applicable). Procedure: Surgical tumor resection Surgical tumor resection on Day 10.
Experimental: Group 3: Cetuximab + IMC-A12 Cetuximab: 400 mg/m2 i.v. over 120 minutes on week 1, and 250 mg/m2 on week 2 and 3 i.v. over 60 minutes. IMC-A12: 6 mg/kg/week i.v. over 1 hour on weeks 1 and 2 and 3.	Drug: Cetuximab First dose of 400 mg/m^2 by vein on Days 1 and 8 over 2 hours, second dose of 250 mg/m^2 on week 2 and 3 (if applicable) given over 1 hour. Other Names: C225 Erbitux IMC-C225 Drug: IMC-A12 6 mg/kg/week by vein on Days 1 and 8 over 1 hour on weeks 1 and 2 and 3 (if applicable). Procedure: Surgical tumor resection Surgical tumor resection on Day 10.

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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 diagnosis of squamous cell carcinoma of the head and neck (excluding carcinomas of the nasopharynx types II and III according to the World Health Organization criteria), for whom surgical resection of the tumor is planned as part of the treatment. Patients with skin squamous cell carcinomas of the head and neck region will also be included in this study.
There is availability of a baseline, paraffin-embedded, tumor specimen for biomarker evaluation. No anti-neoplastic treatment is allowed between the time from obtaining the baseline tumor specimen and randomization. If a baseline tumor specimen is not available, a biopsy of the tumor will be performed prior to randomization.
Prior treatment with biological agents targeted to the epidermal growth factor receptor is allowed, provided the time from last exposure to this treatment was >/= 6 months.
The patient has a fasting serum glucose < 130 mg/dL and HbA1C < 7.0%. Patients with a history of diabetes mellitus are allowed to participate, provided that they are on a stable dietary or therapeutic regimen for this condition.
The patient has adequate renal function, defined by serum creatinine </= 1.5 * the institutional upper limit of normal (ULN), or creatinine clearance >/=60 mL/min for patients with creatinine levels above the ULN.
Because the teratogenicity of cetuximab and IMC-A12 is not known, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
The patient is age >/= 18 years.
The patient or the patient's legally authorized representative has the ability to understand and the willingness to sign a written informed consent document.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

Exclusion Criteria:

Patients receiving any other agent (investigational or not) with potential anti-neoplastic activity within 3 weeks prior to obtaining the baseline tumor specimen for biomarker evaluation.
Patients receiving concomitant radiation.
Prior treatment with an agent targeted at the insulin-like growth factor-1 receptor.
History of allergic reactions attributed to compounds of chemical and biological composition similar to those of cetuximab or IMC-A12.
Pregnant patients, or patients who are breast feeding (patients who have a positive pregnancy test within the first 30 days before the first dose of treatment are excluded).
Patients with uncontrolled illnesses which, in the opinion of the investigator, could be aggravated by the administration of the study drug(s).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00957853

Contacts

Contact: William N. William Jr., MD

713-792-6363

Locations

United States, Texas
UT MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: William N. William Jr., MD

Sponsors and Collaborators

M.D. Anderson Cancer Center

ImClone LLC

Investigators

Study Chair:

William N. William Jr., MD

UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00957853 History of Changes
Other Study ID Numbers:	2008-0342
Study First Received:	August 12, 2009
Last Updated:	February 22, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

Head and Neck Cancer
Squamous cell carcinoma of the head and neck
HNSCC
Cetuximab
IMC-A12

Tumor
Biomarkers
Phospho-AKT
Surgical resection

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
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013