Trial of 2 Cycles of Induction Chemo With Abraxane, Cetuximab, Cisplatin, & 5-FU for Advanced Head and Neck Cancer | RxWiki

Trial of 2 Cycles of Induction Chemo With Abraxane, Cetuximab, Cisplatin, & 5-FU for Advanced Head and Neck Cancer

Overview[ - collapse ][ - ]

Purpose	This phase two trial will determine the tumor response rate at the primary site and at involved regional nodes to two cycles of an IC regimen of weekly Abraxane and cetuximab given in combination with cisplatin and 5-FU in patients with local regionally advanced HNSCC.
Condition	Squamous Cell Carcinoma of the Head and Neck
Intervention	Drug: Abraxane Drug: Cetuximab Drug: Cetuximab Drug: Cisplatin Drug: 5-FU Radiation: Radiation (Post induction) Drug: Cisplatin Drug: Cetuximab
Phase	Phase 2
Sponsor	Washington University School of Medicine
Responsible Party	Washington University School of Medicine
ClinicalTrials.gov Identifier	NCT00736944
First Received	August 13, 2008
Last Updated	March 24, 2014
Last verified	March 2014

Tracking Information[ + expand ][ + ]

First Received Date	August 13, 2008
Last Updated Date	March 24, 2014
Start Date	October 2008
Estimated Primary Completion Date	August 2020
Current Primary Outcome Measures	Clinical Complete Response Rate at the Primary Tumor [Time Frame: post-2 cycles of induction (approximately 42 days from start of treatment)] [Designated as safety issue: No]Clinical exam included laryngoscopy in office or operating room. Complete response rate includes complete response (CR) which is defined as 100% decrease in tumor size and it also includes near complete response (near CR) defined as 95-99% decrease in tumor size.
Current Secondary Outcome Measures	Clinical Partial Response Rate at the Primary Tumor [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]Clinical exam included laryngoscopy in office or operating room. Partial response rate (PR) defined as 50% to 94% decrease in tumor size. Clinical Complete and Partial Response Rates to the Involved Regional Nodes [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]Clinical exam consisted of physical exam of neck in office. Complete response rate includes complete response (CR) which is defined as 100% decrease in tumor size and near complete response (near CR) defined as 95-99% decrease in tumor size. Partial response rate defined as 50% to 94% decrease in tumor size. Clinical Overall Complete and Partial Response Rates [Time Frame: post-2 cycles of induction therapy (approximately 42 days)] [Designated as safety issue: No]Clinical exam included laryngoscopy in office or operating room. Clinical exam consisted of physical exam of neck in office. Complete response rate includes complete response (CR) which is defined as 100% decrease in tumor size and it also includes near complete response (near CR) defined as 95-99% decrease in tumor size. Partial response rate defined as 50% to 94% decrease in tumor size. Complete and Partial Response Rates of Primary Tumor by FDG Uptake on PET Scan [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]Complete response rate defined as complete resolution of the metabolically active primary tumor. Partial response rate defined as 20% or greater decrease in maximum SUV [SUV g/ml) = ROI activity (mCi/ml) / (injected dose (mCi/body weight(g))] from baseline. No unequivocal metabolic progression of non-target disease, and no unequivocal new lesions. Complete and Partial Response Rates of Involved Lymph Nodes by FDG Uptake on PET Scan [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]Complete response rate defined as complete resolution of the metabolically active primary tumor. Partial response rate defined as 20% or greater decrease in maximum SUV [SUV g/ml) = ROI activity (mCi/ml) / (injected dose (mCi/body weight(g))] from baseline. No unequivocal metabolic progression of non-target disease, and no unequivocal new lesions. Radiographic Complete and Partial Response Rates of Primary Tumor as Assessed by Conventional CT Scan Using RECIST Criteria [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]Complete response rate per RECIST criteria is defined as disappearance of all target lesions. Partial response rate per RECIST criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter. Radiographic Complete and Partial Response Rates of Involved Lymph Nodes as Assessed by Conventional CT Scan Using RECIST Criteria [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]Complete response rate per RECIST criteria is defined as disappearance of all target lesions. Partial response rate per RECIST criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter. Radiographic Overall Complete and Partial Response Rates as Assessed by Conventional CT Scan Using RECIST Criteria [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]Complete response rate per RECIST criteria is defined as disappearance of all target lesions. Partial response rate per RECIST criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter. Correlate Primary Tumor Site Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]In the future, primary tumor site, nodal, and OTR by VCR (CR-x or PR-x = Y or N) will be compared with response based on CT scan (CR-x or PR-x = Y or N) using a test for difference in paired, binary values. Median standardized uptake value of FDG measured by PET/CT will be compared among those with or without response (CR-x or PR-x) using nonparametric Wilcoxon-Mann-Whitney tests. We are releasing results based on comparing actual responses from visual categorical response, CT scan, and FDG-PET/CT scan after 2 cycles. Correlate Nodal Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]In the future, primary tumor site, nodal, and overall tumor response by visual categorical response (CR-x or PR-x = yes or no) will be compared with response based on CT scan (CR-x or PR-x = yes or no) using a test for difference in paired, binary values (e.g., McNemar's test). Median standardized uptake value of FDG measured by PET/CT will be compared among those with or without response (CR-x or PR-x) using nonparametric Wilcoxon-Mann-Whitney tests. At this point, we are releasing results based on comparing actual responses from visual categorical response, CT scan, and FDG-PET/CT scan after 2 cycles of induction. Correlate Overall Tumor Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]In the future, primary tumor site, nodal, and overall tumor response by visual categorical response (CR-x or PR-x = yes or no) will be compared with response based on CT scan (CR-x or PR-x = yes or no) using a test for difference in paired, binary values (e.g., McNemar's test). Median standardized uptake value of FDG measured by PET/CT will be compared among those with or without response (CR-x or PR-x) using nonparametric Wilcoxon-Mann-Whitney tests. At this point, we are releasing results based on comparing actual responses from visual categorical response, CT scan, and FDG-PET/CT scan after 2 cycles of induction. Correlate SPARC Expression by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Complete Response Rate to Induction Chemotherapy [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]SPARC expression = Proportion of tumor cells SPARC-positive in 10 high-power fields Correlate SPARC Expression by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Partial Response Rate to Induction Chemotherapy [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]SPARC expression = Proportion of tumor cells SPARC-positive in 10 high-power fields Correlate SPARC Expression (Intensity of Staining) by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Complete Response Rate to Induction Chemotherapy [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]SPARC expression = intensity of SPARC staining in tumor Correlate SPARC Expression (Intensity of Staining) by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Partial Response Rate to Induction Chemotherapy [Time Frame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)] [Designated as safety issue: No]SPARC expression = intensity of SPARC staining in tumor Adverse Events Experienced During Induction Chemotherapy in the First Ten Patients for a Pre-planned Safety Analysis [Time Frame: completion of the first 10 patients induction chemotherapy] [Designated as safety issue: Yes] Overall Survival [Time Frame: 10 years from completion of treatment] [Designated as safety issue: No]Time from diagnosis to death or to last follow-up alive. Disease Free Survival [Time Frame: 10 years from completion of treatment] [Designated as safety issue: No]Time from complete response to death from any cause, to disease progression or to last follow-up alive. Progression-free Survival [Time Frame: 10 years from completion of treatment] [Designated as safety issue: No]Time from initiation of induction chemotherapy to death due to disease progression, to disease progression, or to last follow-up alive.

Descriptive Information[ + expand ][ + ]

Brief Title	Trial of 2 Cycles of Induction Chemo With Abraxane, Cetuximab, Cisplatin, & 5-FU for Advanced Head and Neck Cancer
Official Title	Trial to Determine the CR Rate at the Primary Tumor Site After 2 Cycles of Induction Chemo With Abraxane, Cetuximab, Cisplatin, & 5-FU for Advanced Head & Neck Carcinoma Treated With Definitive Concurrent Cisplatin & Radiation Therapy
Brief Summary	This phase two trial will determine the tumor response rate at the primary site and at involved regional nodes to two cycles of an IC regimen of weekly Abraxane and cetuximab given in combination with cisplatin and 5-FU in patients with local regionally advanced HNSCC.
Detailed Description	Primary objective: To determine the clinical CR rate (CR-p) at the primary tumor site to an IC regimen of weekly Abraxane and cetuximab with CF (ACCF) given for two cycles (over 6 weeks) in patients with locally advanced non-metastatic HNSCC. The assessment of primary tumor site response will be performed by the treating physician by careful clinical examination using WHO criteria. Radiographic studies will also be performed to assess primary tumor site response but will be used primarily to confirm lack of disease progression that may not be detected based on clinical examination alone. The secondary objectives include: - Document the clinical PR rate (PR-p) at the primary tumor site with this IC regimen - Document the clinical CR and PR rates at the involved regional nodes (CR-n and PR-n) with this IC regimen - Document the clinical overall CR rate (CR-o) (defined as achievement of a CR at the primary tumor site and at the involved regional nodes) and the clinical overall PR rate (PR-o) with this IC regimen - Document the CR (CR-p, CR-n, and CR-o) and PR (PR-p, PR-n, and PR-o) rates by FDG uptake on PET scan after this IC regimen - Document radiographic CR (CR-p, CR-n, and CR-o) and PR (PR-p, PR-n, and PR-o) rates as assessed by conventional CT scan using RECIST criteria after this IC regimen. - Correlate primary tumor site, nodal and overall tumor response rates based on WHO criteria of assessment with that based on CT scan and FDG-PET/CT. - Document and quantify SPARC expression by IHC in primary tumor tissue obtained at baseline in each patient and attempt to correlate these results with primary tumor site response to ACCF. - Document and grade AE's with this IC regimen with a pre-planned safety analysis after the first ten patients have completed the IC regimen. - Determine the overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) of this patient population.
Study Type	Interventional
Study Phase	Phase 2
Study Design	Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Squamous Cell Carcinoma of the Head and Neck
Intervention	Drug: Abraxane 100 mg/m2 IVPB, Day 1, 8 and 15 of cycles 1, 2, and 3 Drug: Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1 Drug: Cetuximab 250 mg IVPB, Day 8 and 15 cycle 1, Day 1, 8 and 15 of cycles 2 and 3 Drug: Cisplatin 75 mg/m2 IVPB Day 1, cycles 1, 2 and 3 Drug: 5-FU 750 mg/m2 CIVI Day 1, 2 and 3, cycles 1, 2 and 3 Radiation: Radiation (Post induction) Monday-Friday, weeks 1-7 Drug: Cisplatin (Post induction) Cisplatin 100 mg/m2 IVPB on radiation day 1, 22 and 42 Drug: Cetuximab (Post-induction) Cetuximab (for patients who cannot receive cisplatin) will begin (+/- 3 days) before starting radiation therapy at 400 mg/m2 IVPB. Subsequent doses of cetuximab will be given weekly at 250 mg/m2 IVPB
Study Arm (s)	Experimental: 1 Induction chemotherapy followed by Radiation therapy plus Cisplatin Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42. Experimental: 2 Induction chemotherapy followed by Radiation therapy plus Cetuximab Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cetuximab (for patients who cannot receive cisplatin) will begin (+/- 3 days) before starting radiation therapy at 400 mg/m2 IVPB. Subsequent doses of cetuximab will be given weekly at 250 mg/m2 IVPB

Recruitment Information[ + expand ][ + ]

Recruitment Status	Active, not recruiting
Estimated Enrollment	30
Estimated Completion Date	August 2020
Estimated Primary Completion Date	August 2010
Eligibility Criteria	Inclusion - Selected Stages 3 and 4a/b HNSCC: All patients must have T2-T4 primary tumors. Patients with T1 tumors will be excluded. Although most of these patients will have regional nodal disease, patients with no nodal disease will also be eligible. - Oropharynx, hypopharynx, larynx, and oral cavity sub-sites only. Patients with nasopharyngeal, sinus and other sub-sites of the head and neck, or unknown primary SCC of the head and neck will NOT be eligible. - Age ≥18 years - Signed informed consent. - ECOG Performance Status (PS) of 0-2 (Appendix 1). - Adequate vital organ function (serum creatinine < 1.8 mg/dl, total bilirubin mg/dl, ALT and AST hematopoietic function (ANC >/= 1500/ul, Platelets > 100,000/ul, HGB > 9.0 g/dl). - Patients with reproductive potential must use an effective method of contraception to avoid pregnancy for the duration of the trial and for three months after completing treatment. - If female of childbearing potential, the patient must have a negative pregnancy test. Exclusion Criteria: - Peripheral neuropathy > Grade 1. - Prior chemotherapy, EGFR targeted therapy or radiation therapy for HNSCC. - History of prior invasive malignancy diagnosed within the last three years other than local stage non-melanoma skin cancer. - Be taking cimetidine or allopurinol. Patients must discontinue taking the medication for one week before receiving treatment with Abraxane. - Be taking cimetidine or allopurinol. Patients must discontinue taking the medication for one week before receiving treatment with Abraxane.
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT00736944
Other Study ID Numbers	08-0911 / 201105504
Has Data Monitoring Committee	No
Information Provided By	Washington University School of Medicine
Study Sponsor	Washington University School of Medicine
Collaborators	Not Provided
Investigators	Principal Investigator: Douglas Adkins, M.D. Washington Univerisity
Verification Date	March 2014

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