Combination Chemotherapy and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

This study has been terminated.
(Low dose radiation treatment was not appropriate for these patients.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00352118
First received: July 13, 2006
Last updated: November 6, 2012
Last verified: November 2012
  Purpose

RATIONALE: Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with radiation therapy works in treating patients with locally advanced head and neck cancer. The doctor also wants to find out if patients who receive this treatment need a feeding tube 1 year after starting treatment.


Condition Intervention Phase
Head and Neck Cancer
Biological: filgrastim
Biological: pegfilgrastim
Drug: cisplatin
Drug: docetaxel
Drug: fluorouracil
Procedure: conventional surgery
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Pilot Study of TPF (Docetaxel, Cisplatin, and 5-FU) Induction Chemotherapy Followed by Concurrent Cisplatin and Reduced Dose Radiation in Locally Advanced Head and Neck Cancer

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Number of Patients With Feeding Tube Dependency [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
    All patients were non-evaluable and study was terminated early. There is no measure of outcome.


Secondary Outcome Measures:
  • Number of Days With Progression-free Survival [ Time Frame: Between date of registration to date of first treatment failure or death. ] [ Designated as safety issue: No ]
    All patients were non-evaluable and study was terminated early. There is no measure of outcome. Utilizing RECIST criteria.

  • Number of Days - Overall Survival [ Time Frame: Between date of registration to date of death. ] [ Designated as safety issue: No ]
    All patients were non-evaluable and study was terminated early. There is no measure of outcome. Utilizing RECIST criteria.

  • Number of Days With Disease Free Survival [ Time Frame: From Date of Registration to Date of First Treatment Failure or Death ] [ Designated as safety issue: No ]
    All patients were non-evaluable and study was terminated early. There is no measure of outcome. RECIST criteria measurement.

  • Time to Treatment Failure [ Time Frame: Number of Days from Complete or Partial Response to First Date of Recurrence or Progression ] [ Designated as safety issue: No ]
    All patients were non-evaluable and study was terminated early. There is no measure of outcome. Measure using RECIST criteria.

  • Swallowing Ability - Quality of Life Scores [ Time Frame: Baseline, before chemoradiation, 30 days after last radiation treatment, every 3 months for the first year, then every 6 months for year 2. ] [ Designated as safety issue: No ]
    All patients were non-evaluable and study was terminated early. There is no measure of outcome. Utilizing Swallowing Portion of ASHA Functional Communication Measure for Swallowing (FCM) and Dysphagia Outcome and Severity Scale (DOSS).

  • Quality of Life (QOL) by Functional Assessment of Cancer Therapy-H&N QOL Questionnaire [ Time Frame: baseline, before chemoradiotherapy, 1 month after the last radiation treatment, every 3 months for 1 year, and then every 6 months for 1 year ] [ Designated as safety issue: No ]
    All patients were non-evaluable and study was terminated early. There is no measure of outcome.


Enrollment: 4
Study Start Date: March 2006
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemotherapy + Low Dose Radiation
Patients receiving chemotherapy and Low Dose (60 Gy) Radiation per protocol.
Biological: filgrastim
subcutaneously on Days 5-14, repeating every 3 weeks for 2 courses.
Other Names:
  • G-CSF
  • Neupogen
Biological: pegfilgrastim
If applicable on day 5, repeating every 3 weeks for 2 courses.
Other Name: Neulasta, G-CSF
Drug: cisplatin
Intravenous over 1 hour on day 1, every 3 weeks for 3 courses.
Other Names:
  • CDDP
  • cisplatinum
  • cis-diamminedichloridoplatinum
  • Platinol AQ
Drug: docetaxel
Intravenous over 1 hour on day 1.
Other Name: Taxotere(R)
Drug: fluorouracil
Intravenous continuously on days 1-4.
Other Names:
  • 5-FU
  • 5-fluorouracil
  • Adrucil
Procedure: conventional surgery
As appropriate, neck dissection.
Other Name: surgery
Radiation: radiation therapy
60 Gy 5 days/week x 6 weeks with cisplatin
Other Name: radiation

Detailed Description:

OBJECTIVES:

Primary

  • Determine feeding tube dependency at 12 months in patients with locally advanced head and neck cancer treated with induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil followed by cisplatin and reduced-dose radiotherapy.

Secondary

  • Determine the progression-free, disease-free, and overall survival of patients treated with this regimen.
  • Determine the pattern of failure in patients treated with this regimen.
  • Evaluate the quality of life of patients treated with this regimen.
  • Assess pre- and post-treatment swallowing ability of patients and the impact on their quality of life.

Tertiary

  • Quantify salivary flow rates of patients receiving chemotherapy with radiotherapy for head and neck malignancy.
  • Evaluate the quality of saliva by examining total protein concentrations.
  • Quantify proangiogenic cytokines (interleukin [IL]-1, IL-6, IL-8, and vascular endothelial growth factor) in the saliva of these patients.
  • Determine the degree of mucositis and xerostomia of patients receiving chemotherapy with radiotherapy for head and neck malignancy.
  • Compare salivary flow rates with the grade of mucositis and xerostomia of patients receiving chemotherapy with radiotherapy for head and neck malignancy.

OUTLINE: This is a pilot study.

  • Induction therapy: Patients receive docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1 followed by fluorouracil IV continuously on days 1- 4. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 5-14 or pegfilgrastim SC on day 5. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a partial or clinical complete response proceed to chemoradiotherapy 3 weeks later.
  • Chemoradiotherapy: Patients receive cisplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo concurrent reduced-dose radiotherapy 5 days a week for 6 weeks.
  • Surgery: Approximately 6 to 8 weeks after completing chemoradiotherapy, patients with residual neck disease or disease initially staged at N2 or greater undergo neck dissection.

Saliva is collected periodically to measure flow rates and quality; quantify proangiogenic cytokines (interleukin [IL]-1, IL-6, IL-8 and vascular endothelial growth factor); and examine the grade of mucositis and xerostomia.

Quality of life is assessed at baseline, before chemoradiotherapy, 1 month after the last radiation treatment, every 3 months for 1 year, and then every 6 months for 1 year.

After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed squamous cell carcinoma of the head and neck

    • Stage IVA or IVB disease

      • Stage III disease allowed provided patient may benefit from organ preservation or patient refused surgery
  • Measurable or evaluable disease
  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Creatinine ≤ 1.5 mg/dL OR glomerular filtration rate ≥ 60 mL/min
  • Bilirubin normal
  • Alkaline phosphatase (AP) and AST or ALT must be within the following ranges:

    • AP normal AND AST or ALT ≤ 5 times upper limit of normal (ULN)
    • AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
    • AP ≤ 5 times ULN AND AST or ALT normal

Exclusion Criteria:

  • Salivary gland, sinus, or nasopharyngeal primary disease
  • Evidence of distant metastatic disease
  • Pregnant or nursing
  • Positive pregnancy test (Fertile patients must use effective contraception during study treatment and for 3 months after completion of study treatment)
  • Other malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other malignancy in which stage and nature of disease is such that it is unlikely to affect survival for the next 3 years
  • Peripheral neuropathy ≥ grade 2
  • Hearing loss ≥ grade 2
  • Severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 and/or cisplatin or other platinum analogs
  • Poor nutritional status, in the opinion of the investigator
  • Active infection
  • Active ischemic heart disease
  • Myocardial infarction within the past 6 months
  • Prior radiotherapy above the clavicles
  • Prior chemotherapy
  • Prior surgery to the primary tumor except biopsy
  • Concurrent amifostine or other investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00352118

Locations
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Frank G. Ondrey, MD, PhD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00352118     History of Changes
Other Study ID Numbers: 2005LS012, UMN-0502M67486
Study First Received: July 13, 2006
Results First Received: June 2, 2009
Last Updated: November 6, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:
oral complications of radiation therapy
oral complications of chemotherapy
mucositis
xerostomia
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Docetaxel
Cisplatin
Fluorouracil
Lenograstim
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on April 23, 2014