Clinical trial NCT00736944: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Head and Neck
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2008-08-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 \</= 1.5 mg/dl, ALT and AST \</= 2.5 x ULN, alkaline phosphatase \</= 2.5 x ULN) and 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.

Primary outcomes:
measure: Clinical Complete Response Rate at the Primary Tumor
timeFrame: post-2 cycles of induction (approximately 42 days from start of treatment)
Secondary outcomes:
measure: Clinical Partial Response Rate at the Primary Tumor
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Clinical Complete and Partial Response Rates to the Involved Regional Nodes
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Clinical Overall Complete and Partial Response Rates
timeFrame: post-2 cycles of induction therapy (approximately 42 days)
measure: Complete and Partial Response Rates of Primary Tumor by FDG Uptake on PET Scan
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Complete and Partial Response Rates of Involved Lymph Nodes by FDG Uptake on PET Scan
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Radiographic Complete and Partial Response Rates of Primary Tumor as Assessed by Conventional CT Scan Using RECIST Criteria
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Radiographic Complete and Partial Response Rates of Involved Lymph Nodes as Assessed by Conventional CT Scan Using RECIST Criteria
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Radiographic Overall Complete and Partial Response Rates as Assessed by Conventional CT Scan Using RECIST Criteria
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Correlate Primary Tumor Site Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Correlate Nodal Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Correlate Overall Tumor Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Correlate SPARC Expression by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Complete Response Rate to Induction Chemotherapy
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Correlate SPARC Expression by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Partial Response Rate to Induction Chemotherapy
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Correlate SPARC Expression (Intensity of Staining) by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Complete Response Rate to Induction Chemotherapy
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Correlate SPARC Expression (Intensity of Staining) by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Partial Response Rate to Induction Chemotherapy
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
measure: Adverse Events Experienced During Induction Chemotherapy in the First Ten Patients for a Pre-planned Safety Analysis
timeFrame: completion of the first 10 patients induction chemotherapy
measure: Overall Survival
timeFrame: 10 years from completion of treatment
measure: Disease Free Survival
timeFrame: 10 years from completion of treatment
measure: Time to Progression
timeFrame: 10 years from completion of treatment
Other outcomes:
measure: Overall Complete and Partial Response Rates by FDG Uptake on PET Scan
timeFrame: post-2 cycles of induction therapy (approximately 42 days from start of treatment)
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington Univerisity
name: Douglas Adkins, M.D.
role: PRINCIPAL_INVESTIGATOR
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