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

NCT00671437 | Completed Phase 2 Results

• 1 other identifier: 08-0285 / 201107108
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

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.

Conditions

Carcinoma, Squamous Cell

Keywords

squamous cell carcinoma of the head and neck

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (9)

• Overall Tumor Metabolic Response to Eight Weeks of Scheduled Weekly Doses of Cetuximab as Assessed by FDG-PET/CT

  After 8 weeks of treatment

• Overall Anatomic Response to Eight Weeks of Scheduled Weekly Doses of Cetuximab as Assessed by CT Scan

  After 8 weeks of treatment

• 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

• 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

• 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)

Study Arms (1)

Arm 1

EXPERIMENTAL

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

Procedure: FDG-PET/CT; Drug: Cetuximab

Interventions

FDG-PET/CT PROCEDURE

Arm 1

Cetuximab DRUG

Also known as: Erbitux

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.)

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (2)

University of Louisville

Louisville, Kentucky, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Related Publications (23)

• 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. doi: 10.3322/canjclin.54.1.8.

  PMID: 14974761 BACKGROUND

• 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. doi: 10.1200/JCO.2003.01.504.

  PMID: 12860957 BACKGROUND

• 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. doi: 10.1200/JCO.1993.11.10.1873.

  PMID: 8410112 BACKGROUND

• Ang KK, Berkey BA, Tu X, Zhang HZ, Katz R, Hammond EH, Fu KK, Milas L. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res. 2002 Dec 15;62(24):7350-6.

  PMID: 12499279 BACKGROUND

• Huang S, Armstrong EA, Benavente S, Chinnaiyan P, Harari PM. Dual-agent molecular targeting of the epidermal growth factor receptor (EGFR): combining anti-EGFR antibody with tyrosine kinase inhibitor. Cancer Res. 2004 Aug 1;64(15):5355-62. doi: 10.1158/0008-5472.CAN-04-0562.

  PMID: 15289342 BACKGROUND

• 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. doi: 10.1200/JCO.2003.10.051.

  PMID: 12743152 BACKGROUND

• 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. doi: 10.1056/NEJMoa053422.

  PMID: 16467544 BACKGROUND

• Baselga J, Trigo JM, Bourhis J, Tortochaux J, Cortes-Funes H, Hitt R, Gascon 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. doi: 10.1200/JCO.2005.07.119. Epub 2005 Jul 11.

  PMID: 16009950 BACKGROUND

• 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.

  BACKGROUND

• Vermeersch H, Loose D, Ham H, Otte A, Van de Wiele C. Nuclear medicine imaging for the assessment of primary and recurrent head and neck carcinoma using routinely available tracers. Eur J Nucl Med Mol Imaging. 2003 Dec;30(12):1689-700. doi: 10.1007/s00259-003-1345-4. Epub 2003 Oct 22.

  PMID: 14574516 BACKGROUND

• 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. doi: 10.1200/JCO.2004.08.120.

  PMID: 15514377 BACKGROUND

• 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. doi: 10.1001/archotol.130.12.1361.

  PMID: 15611393 BACKGROUND

• Minn H, Lapela M, Klemi PJ, Grenman 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.

  PMID: 9430467 BACKGROUND

• Brun E, Kjellen 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. doi: 10.1002/hed.10037.

  PMID: 11891942 BACKGROUND

• Weber WA, Ott K, Becker K, Dittler HJ, Helmberger H, Avril NE, Meisetschlager G, Busch R, Siewert JR, Schwaiger M, Fink U. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol. 2001 Jun 15;19(12):3058-65. doi: 10.1200/JCO.2001.19.12.3058.

  PMID: 11408502 BACKGROUND

• 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. doi: 10.1016/s0360-3016(02)03038-9.

  PMID: 12419428 BACKGROUND

• 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.

  PMID: 12163626 BACKGROUND

• 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.

  BACKGROUND

• T. Trarbach et al., A randomized phase I study of the humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody EMD 72000 in subjects with advanced gastrointestinal cancers. J Clinical Oncology 22 (2004), pp. 3018.

  BACKGROUND

• 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. doi: 10.1159/000089765. Epub 2005 Nov 16.

  PMID: 16293972 BACKGROUND

• Antoch G, Kanja J, Bauer S, Kuehl H, Renzing-Koehler K, Schuette J, Bockisch A, Debatin JF, Freudenberg LS. Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors. J Nucl Med. 2004 Mar;45(3):357-65.

  PMID: 15001674 BACKGROUND

• 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.

  PMID: 14734662 BACKGROUND

• Bristol-Meyer-Squibb, Product Information for Erbitux, 2004.

  BACKGROUND

Related Links

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

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Douglas R. Adkins
• Organization: Washington University School of Medicine

dadkins@dom.wustl.edu

314-362-5654

Study Officials

• Douglas Adkins, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2008
• First Posted: May 5, 2008
• Study Start: June 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: August 1, 2015
• Last Updated: March 14, 2017
• Results First Posted: August 10, 2015

Record last verified: 2017-02

Locations

US (2)