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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (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
  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 Intervention Phase
Squamous Cell Carcinoma of the Head and Neck
Drug: Abraxane
Drug: Cetuximab
Drug: Cisplatin
Drug: 5-FU
Radiation: Radiation (Post induction)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

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.



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.


Other Outcome Measures:
  • 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) ] [ 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.



Enrollment: 30
Study Start Date: October 2008
Estimated Study Completion Date: August 2020
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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
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

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: 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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00736944

Locations
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Douglas Adkins, M.D. Washington Univerisity
  More Information

Additional Information:
Publications:

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00736944     History of Changes
Other Study ID Numbers: 08-0911 / 201105504
Study First Received: August 13, 2008
Results First Received: November 18, 2013
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cetuximab
Cisplatin
Fluorouracil
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on August 25, 2014