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NCT Number: NCT00736944

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

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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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Abraxane

Drug

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

Cetuximab

Drug

400 mg/m2 IVPB, Day 1, cycle 1

Cisplatin

Drug

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

5-FU

Drug

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

Radiation (Post induction)

Radiation

Monday-Friday, weeks 1-7

Primary outcomes

  1. Clinical Complete Response Rate at the Primary Tumor

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

    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.

Secondary outcomes

  1. Clinical Partial Response Rate at the Primary Tumor

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

    Clinical exam included laryngoscopy in office or operating room.

    Partial response rate (PR) defined as 50% to 94% decrease in tumor size.

  2. 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)

    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.

  3. Clinical Overall Complete and Partial Response Rates

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

    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.

  4. 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)

    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.

  5. 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)

    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.

  6. 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)

    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.

  7. 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)

    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.

  8. 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)

    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.

  9. 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)

    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.

  10. 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)

    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.

  11. 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)

    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.

  12. 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)

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

  13. 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)

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

  14. 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)

    SPARC expression = intensity of SPARC staining in tumor

  15. 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)

    SPARC expression = intensity of SPARC staining in tumor

  16. 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

  17. Overall Survival

    Time frame: 10 years from completion of treatment

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

  18. Disease Free Survival

    Time frame: 10 years from completion of treatment

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

  19. Time to Progression

    Time frame: 10 years from completion of treatment

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

Other outcomes

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

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

    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.

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Collaborators

  • Celgene Corporation

Registry information

Official study 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

Important dates

Study start
2008
Primary completion
2010
Study completion
2020
First posted
Aug 18, 2008
Registry last updated
Sep 9, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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