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

Carcinoma, Squamous Cell Clinical Trial

— SCCHN  

Official title:

Determination of Tumor SUV by FDG-PET/CT Before and After Cetuximab in Patients With Metastatic Squamous Cell Carcinoma of the Head and Neck

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00671437
• Other study ID #: 08-0285 / 201107108
• Status: Completed
• Phase: Phase 2
• First received: May 1, 2008
• Last updated: August 28, 2015
• Start date: June 2008
• Est. completion date: August 2015

Study information

• Verified date: August 2015
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: August 2015
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms

Intervention

Procedure:
• FDG-PET/CT

Drug:
• Cetuximab

Locations

Country	Name	City	State
United States	University of Louisville	Louisville	Kentucky
United States	Washington University	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (22)

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Antoch G, Saoudi N, Kuehl H, Dahmen G, Mueller SP, Beyer T, Bockisch A, Debatin JF, Freudenberg LS. Accuracy of whole-body dual-modality fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT) for tumor staging in solid tumors: comparison with CT and PET. J Clin Oncol. 2004 Nov 1;22(21):4357-68. — View Citation

Baselga J, Trigo JM, Bourhis J, Tortochaux J, Cortés-Funes H, Hitt R, Gascón P, Amellal N, Harstrick A, Eckardt A. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2005 Aug 20;23(24):5568-77. Epub 2005 Jul 11. — View Citation

Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. — View Citation

Brun E, Kjellén E, Tennvall J, Ohlsson T, Sandell A, Perfekt R, Perfekt R, Wennerberg J, Strand SE. FDG PET studies during treatment: prediction of therapy outcome in head and neck squamous cell carcinoma. Head Neck. 2002 Feb;24(2):127-35. — View Citation

Choi NC, Fischman AJ, Niemierko A, Ryu JS, Lynch T, Wain J, Wright C, Fidias P, Mathisen D. Dose-response relationship between probability of pathologic tumor control and glucose metabolic rate measured with FDG PET after preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2002 Nov 15;54(4):1024-35. — View Citation

Cohen EE, Rosen F, Stadler WM, Recant W, Stenson K, Huo D, Vokes EE. Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol. 2003 May 15;21(10):1980-7. — View Citation

Dassonville O, Formento JL, Francoual M, Ramaioli A, Santini J, Schneider M, Demard F, Milano G. Expression of epidermal growth factor receptor and survival in upper aerodigestive tract cancer. J Clin Oncol. 1993 Oct;11(10):1873-8. — View Citation

Gayed I, Vu T, Iyer R, Johnson M, Macapinlac H, Swanston N, Podoloff D. The role of 18F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal tumors. J Nucl Med. 2004 Jan;45(1):17-21. Erratum in: J Nucl Med. 2004 Nov;45(11):1803. — View Citation

Goldstein D, Tan BS, Rossleigh M, Haindl W, Walker B, Dixon J. Gastrointestinal stromal tumours: correlation of F-FDG gamma camera-based coincidence positron emission tomography with CT for the assessment of treatment response--an AGITG study. Oncology. 2005;69(4):326-32. Epub 2005 Nov 16. — View Citation

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J. Trigo et al., Cetuximab monotherapy is active in patients with platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck: Results of a phase II study (abstract). Proc Am Soc Clin Oncol 23 (2004), p. 487a.

Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ, Thun MJ; American Cancer Society. Cancer statistics, 2004. CA Cancer J Clin. 2004 Jan-Feb;54(1):8-29. Review. — View Citation

Kostakoglu L, Coleman M, Leonard JP, Kuji I, Zoe H, Goldsmith SJ. PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease. J Nucl Med. 2002 Aug;43(8):1018-27. — View Citation

M. Beeram et al., Durable disease stabilization and antitumor activity with OSI-774 in renal cell carcinoma: A phase II, pharmacokinetic (PK) and biological correlative study with FDG-PET imaging. J Clinical Oncology 22 (2004), pp. 3050.

Mendelsohn J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol. 2003 Jul 15;21(14):2787-99. Review. — View Citation

Minn H, Lapela M, Klemi PJ, Grénman R, Leskinen S, Lindholm P, Bergman J, Eronen E, Haaparanta M, Joensuu H. Prediction of survival with fluorine-18-fluoro-deoxyglucose and PET in head and neck cancer. J Nucl Med. 1997 Dec;38(12):1907-11. — View Citation

Schwartz DL, Rajendran J, Yueh B, Coltrera MD, Leblanc M, Eary J, Krohn K. FDG-PET prediction of head and neck squamous cell cancer outcomes. Arch Otolaryngol Head Neck Surg. 2004 Dec;130(12):1361-7. — View Citation

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* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metabolic Response of Target Lesions Assessed as the Change in Standardized Uptake Values (SUV) Max on FDG-PET/CT	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.	Baseline and after 8 weeks of treatment	No
Primary	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.	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.	Baseline and after 8 weeks of treatment	No
Secondary	Overall Tumor Metabolic Response to Eight Weeks of Scheduled Weekly Doses of Cetuximab as Assessed by FDG-PET/CT	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.	After 8 weeks of treatment	No
Secondary	Overall Anatomic Response to Eight Weeks of Scheduled Weekly Doses of Cetuximab as Assessed by CT Scan	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.	After 8 weeks of treatment	No
Secondary	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	A generalization of McNemar's test was used to test for concordance of response(partial, stable or progression) by CT and by FDG-PET/CT.	After 8 weeks of treatment	No
Secondary	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	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.	After 8 weeks of treatment	No
Secondary	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)	No
Secondary	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	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.	Every 8 weeks until disease progression (up to 1 year)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	Yes

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine