Determine Tumor Response Using Fluorodeoxyglucose (FDG)- Positron Emission Tomography (PET)/Computed Tomography (CT) Before and After Cetuximab in Patients With Head and Neck Cancer

Phase 2

Completed

Conditions: Carcinoma, Squamous Cell

Interventions: Procedure: FDG-PET/CT
Drug: Cetuximab

Registration Number: NCT00671437

Lead Sponsor: Washington University School of Medicine

Brief Summary: The purpose of this study is to collect data and evaluate how the tumor is broken down in response to standard of care cetuximab treatment by evaluating the FDG-PET/CT scans, toxicity, see how well the FDG-PET/CT scans predict response to treatment and survival.

Detailed Description: Primary Endpoint

To compare the SUV (standardized uptake value) at up to three target tumor sites as assessed by FDG-PET/CT of eligible patients at baseline and then after eight weeks of treatment with cetuximab.

Secondary Endpoints

* To determine the overall tumor metabolic response (complete metabolic response, partial metabolic response, stable metabolic disease or progressive metabolic disease \[CMR, PMR, SMD, or PMD\]) to eight weeks of scheduled weekly doses of cetuximab as assessed by FDG-PET/CT performed at baseline and then after therapy.

* To correlate the overall tumor metabolic response (CMR, PMR, SMD, or PMD) as assessed by FDG-PET/CT with the anatomic tumor response rate (complete response, partial response, stable disease or progressive disease \[CR, PR, SD, or PD\]) by RECIST criteria as assessed by CT and clinical examination performed after eight weeks of scheduled weekly doses of cetuximab.

* To correlate the overall tumor metabolic response (CMR, PMR, SMD, or PMD) as assessed by FDG-PET/CT and to correlate the overall anatomic tumor response (CR, PR, SD, or PD) by RECIST criteria as assessed by CT and clinical examination obtained at baseline and after eight weeks of treatment with weekly scheduled doses of cetuximab to TTP (time to progression) and OS (overall survival) with cetuximab therapy.

* To determine the overall best anatomic tumor response rate (CR, PR, SD, or PD) to cetuximab given until disease progression as assessed by RECIST criteria using CT and clinical examination.

* To determine the overall disease control rate (CR, PR, and SD) by RECIST criteria as assessed by CT and clinical examination and to determine the TTP and the OS with cetuximab therapy.

* To assess the toxicity profile for standard of care cetuximab given to patients with metastatic squamous cell carcinoma of the head and neck.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 42

Inclusion Criteria

Histologically proven diagnosis of squamous cell carcinoma of the head and neck (SCCHN).
Have either locally recurrent, unresectable, previously irradiated SCCHN OR metastatic SCCHN, with at least one measurable tumor lesion (by CT scan) and at least one FDG avid (SUV >/= 3, >/= 1.5 cm) tumor lesion (by PET/CT).
Age greater than 18 yrs.
ECOG Performance Status of 0-3
Signed IRB approved Informed Consent.

Exclusion Criteria

Clinical history of severe interstitial lung disease (not COPD)-as defined by prior pulmonary function tests (PFTs) with residual volume, total lung capacity, or corrected diffuse lung capacity for carbon monoxide (DLCO) <30% of predicted. For this study, screening PFT's required only if clinically indicated.
Prior therapy with an epidermal growth factor receptor (EGFR)-specific monoclonal antibody (MAB) for treatment of metastatic SCCHN. Prior therapy with an EGFR-specific MAB as part of the definitive treatment of non-metastatic SCCHN is acceptable if this occurred more than three months previously. Prior therapy with an EGFR specific TKI will not be an exclusion factor.
Women of child bearing potential who are current pregnant or breast feeding.
Prior severe (Grade 4) infusion reaction to cetuximab.
A serious uncontrolled medical disorder that in the opinion of the Investigator would impair the ability of the subject to receive protocol therapy.
Chemotherapy, radiation therapy, or investigational agents given with the last 14 days.
Uncontrolled diabetes mellitus. (Subjects with a fasting blood glucose > 200 at time of PET scanning may need to reschedule to another day after consulting with appropriate physicians.)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1	FDG-PET/CT	Whole body FDG-PET/CT scan and CT scan of neck and chest (within 28 days of Day 1) Cetuximab 400 mg/m2 intravenously (IV) over 2 hours on day 1 and 250 mg/m2 IV over 1 hour on days 8, 15, 22, 29, 36, 43, and 50. Whole Body FDG-PET/CT scan and CT scan of neck and chest on Day 57 (prior to cetuximab infusion) Cetuximab 250 mg/m2 IV over 1 hour on Day 57 Cetuximab 250 mg/m2 IV over 1 hour weekly until progressive disease
Arm 1	Cetuximab	Whole body FDG-PET/CT scan and CT scan of neck and chest (within 28 days of Day 1) Cetuximab 400 mg/m2 intravenously (IV) over 2 hours on day 1 and 250 mg/m2 IV over 1 hour on days 8, 15, 22, 29, 36, 43, and 50. Whole Body FDG-PET/CT scan and CT scan of neck and chest on Day 57 (prior to cetuximab infusion) Cetuximab 250 mg/m2 IV over 1 hour on Day 57 Cetuximab 250 mg/m2 IV over 1 hour weekly until progressive disease

Primary Outcome Measures

Name	Time	Method
Metabolic Response of Target Lesions Assessed as the Change in Standardized Uptake Values (SUV) Max on FDG-PET/CT	Baseline and after 8 weeks of treatment	FDG-PET/CT images were evaluated qualitatively as well as quantitatively by one of two experienced nuclear radiologists. For quantitative analysis, SUVmax within each of the metastatic tumor sites was determined within a volume of interest around the tumor using a Siemens eSoft workstation. Up to a maximum of three target lesions(\>= 1.5 cm on the baseline CT) were identified as target lesions on the baseline FDG-PET. When multiple lesions were present, those having the greatest FDG uptake on the baseline FDG-PET were selected as target lesions. Lesions containing areas of necrosis were avoided. Other metabolically active lesions and lesions that were \<1.5 cm on CT were considered non-target lesions. When more than one target lesion was identified, the average percentage change in SUVmax was used to determine metabolic response.
SUVmax at up to Three Target Tumor Sites as Assessed by FDG-PET/CT of Eligible Patients at Baseline and Then After Eight Weeks of Treatment With Cetuximab.	Baseline and after 8 weeks of treatment	Eight weeks of treatment is equal to one cycle of treatment. FDG-PET/CT images were evaluated qualitatively as well as quantitatively by one of two experienced nuclear radiologists. For quantitative analysis, SUVmax within each of the metastatic tumor sites was determined within a volume of interest around the tumor using a Siemens eSoft workstation. Up to a maximum of three target lesions(\>= 1.5 cm on the baseline CT) were identified as target lesions on the baseline FDG-PET. When multiple lesions were present, those having the greatest FDG uptake on the baseline FDG-PET were selected as target lesions. Lesions containing areas of necrosis were avoided. Other metabolically active lesions and lesions that were \<1.5 cm on CT were considered non-target lesions. When more than one target lesion was identified, the average percentage change in SUVmax was used to determine metabolic response.

Secondary Outcome Measures

Name	Time	Method
Overall Tumor Metabolic Response to Eight Weeks of Scheduled Weekly Doses of Cetuximab as Assessed by FDG-PET/CT	After 8 weeks of treatment	Definitions of metabolic response by FDG-PET/CT included: complete metabolic response(CMR)-complete resolution of all metabolically active target and non-target lesions, and no new lesions; partial metabolic response(PMR)-20% or greater decrease in SUV of target lesions with or without decrease in number/size of non-target lesions, and no new lesions; progressive metabolic disease(PMD)-one or more new lesions, 20% or greater increase in SUV of target lesions and/or unequivocal increase in FDG activity of non-target lesions; and stable metabolic disease(SMD)-not qualifying as CMR, PMR, or PMD.
Correlate the Overall Tumor Metabolic Response and Overall Anatomic Tumor Response and Clinical Examination Obtained at Baseline and After Eight Weeks of Treatment With Cetuximab to Time to Progression (TTP) With Cetuximab Therapy	Every 8 weeks until disease progression (up to 1 year)	Cetuximab was continued after cycle 1 in patients with disease control(PR/SD) by CT, even if the FDG-PET/CT showed PMD. Cetuximab was discontinued after cycle 1 in patients with progression by CT.
Assess the Toxicity Profile for Standard of Care Cetuximab Given to Patients With Metastatic Squamous Cell Carcinoma of the Head and Neck	30 days after end of study treatment (approximately 1 year after start of treatment)
Determine the Overall Disease Control Rate by RECIST Criteria as Assessed by CT and Clinical Examination and to Determine the TTP and the OS With Cetuximab Therapy	Every 8 weeks until death (approximately 5 years)
Overall Anatomic Response to Eight Weeks of Scheduled Weekly Doses of Cetuximab as Assessed by CT Scan	After 8 weeks of treatment	Definitions of anatomic response by RECIST for CT scan included: complete response(CR)-disappearance of all target and non-target lesions and no new lesions; partial response(PR)-at least 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter, persistence of one or more non-target lesions, and no new lesions; stable disease (SD)-neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum longest diameter since the treatment started, persistence of one or more non-target lesions, and no new lesions; progressive disease(PD)-at least a 20% increase in the sum of the longest diameter of target lesions recorded since the treatment started, appearance of one or more new lesions/unequivocal progression of existing non-target lesions.
Correlation of Overall Tumor Metabolic Response as Assessed by FDG-PET/CT With the Anatomic Tumor Response Rate by RECIST Criteria as Assessed by CT and Clinical Examination	After 8 weeks of treatment	Agreement in treatment decision using CT and FDG-PET/CT. Agreement in treatment decision occurred when tumor response by CT and FDG-PET/CT resulted in the same decision in treatment (continue cetuximab due to disease control or stop cetuximab due to progression). Disagreement in treatment decision occurred when tumor response assessment by CT and FDG-PET/CT resulted in different treatment decisions.
Overall Best Anatomic Tumor Response Rate to Cetuximab Given Until Disease Progression as Assessed by RECIST Criteria Using CT & Clinical Examination	Every 8 weeks until disease progression (up to 1 year)
Correlate the Overall Tumor Metabolic Response and Overall Anatomic Tumor Response and Clinical Examination Obtained at Baseline and After Eight Weeks of Treatment With Cetuximab to Overall Survival With Cetuximab Therapy	Every 8 weeks until death (approximately 5 years)