Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Cetuximab

Fluorouracil

Albumin-Bound Paclitaxel

Cisplatin

Antineoplastic Agents, Immunological

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.

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

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

Abraxane

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

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

5-FU

Radiation (Post induction)

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

(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

Douglas Adkins, M.D.

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.

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.

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

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

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.

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.

Clinical exam included laryngoscopy in office or operating room.

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

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 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 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.

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.

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.

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

SPARC expression = intensity of SPARC staining in tumor

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

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

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

Celgene Corporation

Washington University School of Medicine

Serious adverse events are events grade 3 or higher.

Lab results, treatment records, and dictations reviewed weekly.

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 or Cetuximab 250 mg/m2 IVPB weekly Q8W.

Induction Chemo + RT + Cisplatin or Cetuximab

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Douglas R. Adkins

All patients who completed 2 cycles of induction therapy.

Clinical Complete Response Rate at the Primary Tumor

Participants who completed 2 cycles of induction therapy

Clinical Partial Response Rate at the Primary Tumor

Complete response

Partial response

Twelve patients were not evaluable because of initial absence of nodal disease on clinical exam.

Clinical Complete and Partial Response Rates to the Involved Regional Nodes

Overall complete response

Overall partial response

Clinical Overall Complete and Partial Response Rates

Two patients were not evaluable for this outcome. One patient's insurance company denied coverage for the PET scan so the PET scan was not performed. The other patient only had neck nodes that were clearly measurable on the PET scan, the primary site could not be measured on the PET scan.

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

Five patients were not evaluable for this outcome because these patients did not have any involved lymph nodes that could be measured.

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

Two patients were not evaluable for this outcome. The first patient didn't have primary site disease that could be measured by RECIST. The second patient had primary site disease but it could not be clearly measured by CT. This disease was noted as a non-target lesion as present at baseline.

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

Six patients were not evaluable for this outcome. Five of these patients did not have any involved lymph nodes available to evaluate. The sixth patient did not have involved lymph nodes that were clearly measurable by CT and RECIST.

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

One patient was not evaluable for this outcome. This patient had primary site disease that could not be clearly measured per CT and was listed as a non-target lesion.

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

Complete Response

Partial Response

Stable Disease/Progressive Disease

Clinical Examination

CT Scan

FDG-PET/CT

2 patients were not evaluable for the CT Scan of this outcome because they did not have primary disease that could be measured per RECIST. 2 patients were not evaluable for PET scan of this outcome because one patient's insurance company denied coverage and the other patient did not have primary site disease.

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

12 patients were not evaluable for VSR because they did not have nodal disease. 6 patients were not evaluable for CT scan because 5 patients did not have nodal disease and 1 patient didn't have measurable nodal disease. 5 patients were not evaluable for PET because 5 patients did not have nodal disease.

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

1 patient was not evaluable for CT scan because the primary site could not be clearly measured and was noted as non-target lesion. 1 patient was not evaluable for PET scan because the patient's insurance company denied coverage.

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

Negative staining

1+ staining (0%-24%)

2+ staining (25%-49%)

3+ staining (50%-74%)

4+ staining (75%-100%)

Patients who had available tumor tissue for SPARC testing and were complete responders.

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

Patients who had available tumor tissue for SPARC testing and were partial responders.

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

1+ staining (weak)

2+ staining (moderate)

3+ staining (strong)

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

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

Allergic reaction/hypersensitivity

Other allergic reaction:cipro

Other allergic reaction:hives

Hypotension

Fatigue

Alopecia

Chelitis

Dry skin

Rash

Rash:acneiform

Rash:penile (unconfirmed HSV)

Anorexia

Colitis

Constipation

Dehydration

Dental:teeth

Diarrhea

Hemorrhoids

Nausea

Taste alteration

Vomiting

Other:soft stools

Hemoglobin

Leukocytes (WBC)

Lymphopenia

Neutrophils (ANC)

Platelets

Hemmorrhage:nose

Alkaline phosphatase

SGPT (ALT)

Infection other:sinus infection

Edema:limb

Albumin, low

Calcium, low

Magnesium, low

Potassium, low

Potassium, high

Sodium, low

Phosphorus

Dizziness

Mood alteration:anger

Neuropathy:sensory (peripheral)

Vision-photophobia

Pain:thigh

Pain:tumor pain

Hiccoughs (hiccups)

Obstruction/stenosis of airway:trachea

Creatinine

Renal failure

Thrombosis/thrombus/embolism

Adverse Events Experienced During Induction Chemotherapy in the First Ten Patients for a Pre-planned Safety Analysis

Overall Survival

Disease Free Survival

Time to Progression

One patient was not evaluable for this outcome. This patient's insurance company denied coverage for the post-cycle 2 timepoint and because of this was not included in this overall response rate for PET scan.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Trial of 2 Cycles of Induction Chemo With Abraxane, Cetuximab, Cisplatin, & 5-FU for Advanced Head and Neck Cancer	NCT00736944	Squamous Cell C...	Abraxane Cetuximab Cetuximab Cisplatin 5-FU Radiation (Post... Cisplatin Cetuximab	18 Years -	Washington University School of Medicine
Trial of 2 Cycles of Induction Chemo With Abraxane, Cetuximab, Cisplatin, & 5-FU for Advanced Head and Neck Cancer	NCT00736944	Squamous Cell C...	Abraxane Cetuximab Cetuximab Cisplatin 5-FU Radiation (Post... Cisplatin Cetuximab	18 Years -	Washington University School of Medicine

Spots Global Cancer Trial Database for radiation (post induction)