Have you or your loved ones been diagnosed with squamous cell carcinoma of the head and neck?

You may be eligible to participate in a squamous cell carcinoma of the head and neck clinical trial.

Have you or your loved ones been diagnosed with squamous cell carcinoma of the head and neck? You may be eligible to participate in a squamous cell carcinoma of the head and neck clinical trial.

What is a clinical trial? Is participating in a clinical trial right for you? Learn more

Squamous Cell Carcinoma of the Head and Neck Clinical Trial

NCT00736944 | Phase 2 | Interventional

Have you or your loved ones been diagnosed with squamous cell carcinoma of the head and neck?

You may be eligible to participate in a squamous cell carcinoma of the head and neck clinical trial.

Have you or your loved ones been diagnosed with squamous cell carcinoma of the head and neck? You may be eligible to participate in a squamous cell carcinoma of the head and neck clinical trial.

Completed

Male & Female

18 Years +

This study has recruited 30 Participants

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.

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Details for the study

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<br /> involved regional nodes to two cycles of an IC regimen of weekly Abraxane and cetuximab given<br /> 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.

Treatments and/or Procedures

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

Cisplatin

(Post induction) Cisplatin 100 mg/m2 IVPB on radiation day 1, 22 and 42

5 FU

750 mg/m2 CIVI Day 1, 2 and 3, cycles 1, 2 and 3

Cisplatin

75 mg/m2 IVPB Day 1, cycles 1, 2 and 3

Cetuximab

250 mg IVPB, Day 8 and 15 cycle 1, Day 1, 8 and 15 of cycles 2 and 3

Cetuximab

400 mg/m2 IVPB, Day 1, cycle 1

Abraxane

100 mg/m2 IVPB, Day 1, 8 and 15 of cycles 1, 2, and 3

Radiation post induction

Monday-Friday, weeks 1-7

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.

Primary

Clinical Complete Response Rate at the Primary Tumor

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.

post-2 cycles of induction (approximately 42 days from start of treatment)

Secondary

Time to Progression

Time from initiation of induction chemotherapy to death due to disease progression, to disease progression, or to last follow-up alive.

10 years from completion of treatment

Secondary

Disease Free Survival

Time from complete response to death from any cause, to disease progression or to last follow-up alive.

10 years from completion of treatment

Secondary

Overall Survival

Time from diagnosis to death or to last follow-up alive.

10 years from completion of treatment

Secondary

Correlate SPARC Expression (Intensity of Staining) by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Partial Response Rate to Induction Chemotherapy

SPARC expression = intensity of SPARC staining in tumor

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Correlate Overall Tumor Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT

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.

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Correlate SPARC Expression by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Partial Response Rate to Induction Chemotherapy

SPARC expression = Proportion of tumor cells SPARC-positive in 10 high-power fields

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Correlate SPARC Expression by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Complete Response Rate to Induction Chemotherapy

SPARC expression = Proportion of tumor cells SPARC-positive in 10 high-power fields

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Correlate Nodal Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Correlate Primary Tumor Site Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT

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.

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Radiographic Overall Complete and Partial Response Rates as Assessed by Conventional CT Scan Using RECIST Criteria

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.

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Radiographic Complete and Partial Response Rates of Involved Lymph Nodes as Assessed by Conventional CT Scan Using RECIST Criteria

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Radiographic Complete and Partial Response Rates of Primary Tumor as Assessed by Conventional CT Scan Using RECIST Criteria

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Complete and Partial Response Rates of Involved Lymph Nodes by FDG Uptake on PET Scan

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.

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Complete and Partial Response Rates of Primary Tumor by FDG Uptake on PET Scan

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Clinical Complete and Partial Response Rates to the Involved Regional Nodes

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.

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Clinical Partial Response Rate at the Primary Tumor

Clinical exam included laryngoscopy in office or operating room. Partial response rate (PR) defined as 50% to 94% decrease in tumor size.

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Correlate SPARC Expression (Intensity of Staining) by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Complete Response Rate to Induction Chemotherapy

SPARC expression = intensity of SPARC staining in tumor

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Secondary

Clinical Overall Complete and Partial Response Rates

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.

post-2 cycles of induction therapy (approximately 42 days)

Other

Overall Complete and Partial Response Rates by FDG Uptake on PET Scan

post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Study 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.