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Paclitaxel, Carboplatin And Low Dose Radiation As Induction Therapy In Locally Advanced Head And Neck Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Susanne Arnold, University of Kentucky
ClinicalTrials.gov Identifier:
NCT00176267
First received: September 9, 2005
Last updated: December 4, 2013
Last verified: December 2013

September 9, 2005
December 4, 2013
September 2002
February 2014   (final data collection date for primary outcome measure)
  • Response rate [ Time Frame: assessed at baseline and once between days 42 and 56, then repeated every 6 months until disease progression ] [ Designated as safety issue: No ]
  • Pathologic complete responses [ Time Frame: assessed between 3 and 24 hours after the last dose of radiation ] [ Designated as safety issue: No ]
  • Pathologic complete responses-assessed between 3 and 24 hours after the last dose of radiation.
  • Response rate-assessed at baseline and once between days 42 and 56, then repeated every 6 months until disease progression.
Complete list of historical versions of study NCT00176267 on ClinicalTrials.gov Archive Site
  • Toxicity [ Time Frame: assessed starting day 1 through study completion day 56 or until toxicities resolve ] [ Designated as safety issue: Yes ]
  • Quality of Life [ Time Frame: assessed pre-study and once between study days 42 and 56 ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: throughout study treatment duration and then every 3 months after study completion ] [ Designated as safety issue: No ]
  • Toxicity-assessed starting day 1 through study completion day 56 or until toxicities resolve.
  • Quality of Life- assessed pre-study and once between study days 42 and 56.
  • Overall survival- throughout study treatment duration and then every 3 months after study completion.
Not Provided
Not Provided
 
Paclitaxel, Carboplatin And Low Dose Radiation As Induction Therapy In Locally Advanced Head And Neck Cancer
Paclitaxel, Carboplatin And Low Dose Radiation As Induction Therapy In Locally Advanced Head And Neck Cancer

This study is being performed utilizing two cycles of Paclitaxel and Carboplatin, plus low doses radiation as initial therapy prior to other treatment (surgery or radiation). The study is assessing if utilization of low doses radiation as a chemoenhancer will further increase the response rate seen with initial therapy.

Squamous cell cancers of the head and neck (SCCHN) comprise 5% of all cancers, with 40,000 new cases diagnosed annually. Surgery followed by irradiation or irradiation alone has been the standard of care for locally advanced Stage III and IV patients. With this approach, fewer than 30% of patients achieve long-term remission, and most recur locoregionally. Neoadjuvant chemotherapy has been administered prior to definitive therapy with response rates ranging from 60-90%, with pathologic CR rates documented in 30-70% of clinical responders. However, large randomized trials have shown no improvement in overall survival. Because induction chemotherapy alone does not appear to improve long-term disease free survival in advanced head and neck cancers, concomitant chemotherapy and radiation has been pursued in patients with locally advanced head and neck cancers. The concept of synergy between radiation and chemotherapy is well established in vitro. Various schedules of radiation and chemotherapy have been utilized including weekly chemotherapy during radiation, chemotherapy given every three weeks during radiation and alternating chemotherapy and radiation.

One novel approach to capitalizes on the synergy between radiation and chemotherapy is the use of low doses fractionated radiation (LDFRT) as a chemotherapy enhancer. In vitro data suggests that LDFRT enhances the response of both p53 wild type and p53 mutant cancer cell lines to chemotherapy. Not only was the cell death fraction increased, but there was no development of radioresistance in the cell lines studies when low doses of radiation were utilized. This strategy was translated into a clinical trial using four 80-cGy fractions of radiation with Carboplatin and Paclitaxel. Preliminary results have produced an impressive 85% response rate and this neoadjuvant regimen was safe and easy to deliver in patients with locally advanced SCCHN patients. In recently published work by Belani, a regimen using Carboplatin every four weeks combined with weekly Paclitaxel improved response rates in non-small cell lung cancer. The delivery of chemotherapy on a weekly schedule would be of particular benefit when adding LDFRT, because tumor cells could be exposed to LDFRT on multiple occasions per cycle of induction therapy, without the theoretic development of radioresistance. We propose to expand our understanding of LDFRT and chemotherapy by using two cycles of Paclitaxel and Carboplatin in a modification of the Belani regimen, plus LDFRT as induction therapy prior to definitive treatment (surgery or radiation). It is hoped that using LDFRT as a chemoenhancer will further increase the response rate seen with induction therapy in this population of patients.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Squamous Cell Carcinoma
  • Radiation: Radiotherapy
    50 cGy on days 1, 2, 8, 15, 22, 23, 29 & 36 of chemotherapy
  • Drug: Paclitaxel
    75 mg/m2 intravenously over one hour on Days 1, 8, 15, 22, 29 and 36
  • Drug: Carboplatin
    AUC of 6 on Days 1 & 22
Experimental: 1
Interventions:
  • Radiation: Radiotherapy
  • Drug: Paclitaxel
  • Drug: Carboplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
40
February 2014
February 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Adult patients greater than 18 years of age.
  2. ECOG performance status of 0, 1 or 2.
  3. Patients with pathologically documented bulky T2, III and IV SCCHN (excluding M1 disease), within 2 months of diagnosis. Bulky T2 tumors are defined as those that have a volume of disease greater than 35 cm3 as measured by CT or MRI scan (28).
  4. Patients will be medically fit for undergoing chemotherapy. Specifically:

    1. no evidence of active angina pectoris or ventricular arrhythmia's; no myocardial infarction within the last six months. (Patients with medically controlled hypertension or congestive heart failure are eligible.)
    2. an absolute neutrophil count of > 1000/uL and platelet count > 100,000/uL
    3. serum total bilirubin < 1.5 mg/dL
    4. Creatinine Clearance greater than 60 ml/min

      Using an actual or calculated creatinine clearance using the formula:

      (140 - age)x(wgt in kg)*/(serum creatinine)x(72)* multiply by 0.85 for females

    5. if a pre-existing grade I neuropathy exists, patients must be willing to risk worsening neuropathy secondary to Paclitaxel. Patients with grade II or greater neuropathy will be excluded from study.
    6. ability to give written, informed consent to participate in the trial.
  5. Patients will have measurable disease as determined by MRI or CT scan or evaluable disease determined by panendoscopy or indirect laryngoscopy to be eligible for enrollment on this study.

Exclusion Criteria:

  1. Pregnant females. Males and women of childbearing potential must use effective contraception in order to prevent pregnancy during therapy.
  2. Patients with a history of previous or current malignancy at other sites diagnosed within the last 5 years, with the exception of adequately treated carcinoma in-situ of the cervix or basal or squamous cell carcinoma of the skin. Patients with a history of other malignancies, who remain free of recurrence or metastases for greater than five years are eligible.
  3. Patients with active infection will not be eligible for this protocol until the infection is treated and the symptoms have clinically resolved.
  4. Patients with a history of allergy to drugs utilizing Cremophor in the formulation.
  5. Prior chemotherapy, prior irradiation or surgery for SCCHN will not be allowed.
  6. Patients with metastatic disease will not be eligible for this study.
  7. Patients with grade II or greater peripheral neuropathy will be excluded from study.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00176267
02-H&N-15-BMS
No
Susanne Arnold, University of Kentucky
Susanne Arnold
Bristol-Myers Squibb
Principal Investigator: Susanne Arnold, MD University of Kentucky
University of Kentucky
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP