Radiation Therapy Cisplatin With or Without Fluorouracil Patients With Stage III or Stage IV Head and Neck Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00608205
First received: January 30, 2008
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as 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. Giving radiation therapy together with cisplatin and fluorouracil may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without fluorouracil in treating patients with head and neck cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy and cisplatin to compare how well they work with or without fluorouracil in treating patients with stage III or stage IV head and neck cancer.


Condition Intervention Phase
Head and Neck Cancer
Drug: cisplatin
Drug: fluorouracil
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial Comparing Single Agent Cisplatin With the Combination of 5-Fluorouracil and Cisplatin, Concurrent With Radiation Therapy in Stage III and IV Squamous Cell Head and Neck Cancer

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Relapse Free Survival [ Time Frame: at 2 yrs from start of study ] [ Designated as safety issue: No ]
    Number of patients that are alive without recurrence.


Secondary Outcome Measures:
  • Patterns of Failure [ Time Frame: 2 years from start of study ] [ Designated as safety issue: No ]
    Patients with any new evidence of cancer after achieving a complete response are considered to have recurrent disease. Biopsy verification will be obtained if at all possible and salvage surgery is recommended if possible. Disease recurrence will be characterized as either local, regional(nodal) or distant recurrence. Patients may have more than one kind of recurrence.

  • Overall Survival [ Time Frame: 2 yrs from start of study ] [ Designated as safety issue: No ]
    Number of patients still alive from 5 years from start of study

  • Number of Patients With a Clinical Response-complete Disappearance of Detectable Tumor [ Time Frame: at 12 weeks after completing chemoradiotherapy ] [ Designated as safety issue: No ]
    Twelve weeks after completing chemoradiotherapy, a formal evaluation for response will be made, to include a careful evaluation by the head and neck surgeon, medical and radiation oncologists, and, as appropriate, a radiologic and an endoscopic examination. Patients will be considered to have achieved either a clinical complete response (i.e. complete disappearance of all clinically and radiologically detectable tumor) or to have clinical persistent disease.

  • Number of Patients With a Pathological(Final)Complete Response [ Time Frame: at 12 weeks after completing chemoradiotherapy and surgery ] [ Designated as safety issue: No ]
    A Pathological, of final response will be assigned to patients after any salvage surgery is performed for clinical persistent disease, and after planned neck dissection in those achieving a clinical complete response. If no surgery is performed after chemoradiotherapy, the clinical and pathological (final) response will be the same. Patient will be coded as having either a pathologic complete response, or as having pathologic persistent disease.

  • Disease Recurrence [ Time Frame: 2 years after start of study ] [ Designated as safety issue: No ]
    Number of patients with any new evidence of cancer after achieving a complete response (at 12 weeks after completing chemoradiotherapy) are considered to have recurrent disease.

  • Number of Patients That Required a Feeding Tube [ Time Frame: 12 weeks (after treatment) ] [ Designated as safety issue: No ]
  • Number of Patients That Required a Feeding Tube [ Time Frame: 8 months after start of treatment ] [ Designated as safety issue: No ]
  • Number of Patients That Required a Feeding Tube [ Time Frame: 12 months after start of treatment ] [ Designated as safety issue: No ]
  • Number of Patients That Required a Feeding Tube [ Time Frame: 24 months after start of treatment ] [ Designated as safety issue: No ]
  • Nausea Level [ Time Frame: 12 weeks (after treatment) ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I have nausea".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.

    N (number of patients analyzed) is based on number of patients who completed the question.


  • Nausea Level [ Time Frame: 8 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I have nausea".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Nausea Level [ Time Frame: 12 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I have nausea".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Nausea Level [ Time Frame: 24 months from start of treatment ] [ Designated as safety issue: No ]
    Quality of life questionnaire asking "I have nausea".

  • Dry Mouth [ Time Frame: 12 weeks (after treatment) ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "My mouth is dry".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Dry Mouth [ Time Frame: 8 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "My mouth is dry".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Dry Mouth [ Time Frame: 12 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "My mouth is dry".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Dry Mouth [ Time Frame: 24 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "My mouth is dry".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Pain [ Time Frame: 12 weeks (after treatment) ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I have pain in my mouth, throat or neck".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Pain [ Time Frame: 8 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I have pain in my mouth, throat or neck".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Pain [ Time Frame: 12 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I have pain in my mouth, throat or neck".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Pain [ Time Frame: 24 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I have pain in my mouth, throat or neck".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Quality of Life [ Time Frame: 12 weeks (after treatment) ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I am content with the quality of my life right now".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Quality of Life [ Time Frame: 8 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I am content with the quality of my life right now".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Quality of Life [ Time Frame: 12 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I am content with the quality of my life right now".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Quality of Life [ Time Frame: 24 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I am content with the quality of my life right now".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Eating [ Time Frame: 12 weeks (after treatment) ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I am able to eat the foods i like".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Eating [ Time Frame: 8 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I am able to eat the foods i like".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Eating [ Time Frame: 12 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I am able to eat the foods i like".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Eating [ Time Frame: 24 months from start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I am able to eat the foods i like".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Swallowing [ Time Frame: 12 weeks (after treatment) ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I can swallow naturally and easily".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Swallowing [ Time Frame: 8 months after start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I can swallow naturally and easily".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Swallowing [ Time Frame: 12 months after start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I can swallow naturally and easily".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Swallowing [ Time Frame: 24 months after start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I can swallow naturally and easily".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Alcohol Consumption [ Time Frame: 12 weeks (after treatment) ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I drink alcohol (e.g. beer, wine)".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Alcohol Consumption [ Time Frame: 8 months after start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I drink alcohol (e.g. beer, wine)".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Alcohol Consumption [ Time Frame: 12 months after start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I drink alcohol (e.g. beer, wine)".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Alcohol Consumption [ Time Frame: 24 months after start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I drink alcohol (e.g. beer, wine)".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Solid Foods [ Time Frame: 12 weeks (after treatment) ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I can eat solid foods".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Solid Foods [ Time Frame: 8 months after start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I can eat solid foods".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Solid Foods [ Time Frame: 12 months after start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I can eat solid foods".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.


  • Solid Foods [ Time Frame: 24 months after start of treatment ] [ Designated as safety issue: No ]

    Quality of life questionnaire asking "I can eat solid foods".

    The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined for each statement.



Enrollment: 69
Study Start Date: January 2008
Estimated Study Completion Date: July 2015
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients undergo full-dose radiotherapy once or twice daily 5 days a week for up to 7 weeks and receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy.
Drug: cisplatin
Given IV
Other Name: CDDP
Radiation: radiation therapy
Patients undergo full-dose radiotherapy once or twice daily 5 days a week for up to 7 weeks
Other Name: radiation
Experimental: Arm II
Patients undergo radiotherapy as in arm I and receive fluorouracil IV and cisplatin IV continuously on days 1-4 and 22-25 of radiotherapy.
Drug: cisplatin
Given IV
Other Name: CDDP
Drug: fluorouracil
Given IV
Other Name: fluorouracil
Radiation: radiation therapy
Patients undergo full-dose radiotherapy once or twice daily 5 days a week for up to 7 weeks
Other Name: radiation

Detailed Description:

OBJECTIVES:

  • To compare the relapse-free survival of patients treated with radiotherapy and cisplatin with vs without fluorouracil.
  • To compare the overall survival, local control without surgery, and patterns of failure in patients treated with these regimens.
  • To compare the acute and long-term toxicity of these regimens in these patients.
  • To compare the quality of life of patients treated with these regimens.
  • To prospectively collect biopsy material, mucosal scrapings, and serum in an effort to generate hypotheses for future correlative studies.

OUTLINE: This is a multicenter study. Patients are stratified according to radiotherapy schedule (once daily vs twice daily) and radiotherapy planning (2D vs 3D vs intensity-modulated radiotherapy). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo full-dose radiotherapy once or twice daily 5 days a week for up to 7 weeks and receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy.
  • Arm II: Patients undergo radiotherapy as in arm I and receive fluorouracil IV and cisplatin IV continuously on days 1-4 and 22-25 of radiotherapy.

Patients with biopsy-verified residual disease at the primary site or local recurrence after achieving a complete response to chemoradiotherapy may undergo salvage surgery 12 weeks after the completion of chemoradiotherapy.

Patients complete questionnaires periodically to assess late toxicity and quality of life.

After completion of study treatment, patients are followed periodically.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx

    • No histologic diagnosis other than squamous cell carcinoma
    • A primary site must be identified
  • Must have locoregionally confined stage III (excluding T1-2, N1) or stage IV disease

    • No evidence of nodal disease below the clavicles or distant hematogenous metastases (M0)
    • No stage IVC disease (stage IVB disease allowed)
  • Deemed appropriate for definitive non-operative management with curative intent

    • Resectable disease is not required
  • No primary cancer of the nasopharynx, paranasal sinus, or salivary gland

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • WBC > 3,500/mm³
  • Platelet count > 100,000/mm³
  • Serum creatinine < 2.0 mg/dL
  • Alkaline phosphatase < 2 times normal
  • AST < 2 times normal
  • Bilirubin ≤ 2.0 mg/dL
  • Serum calcium normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No unstable or uncontrolled angina
  • No clinically apparent jaundice
  • No active infection
  • No history of any other malignancy (except squamous cell or basal cell skin cancer or cervical carcinoma in situ), unless the patient has been continuously disease-free for at least 5 years
  • Not a poor compliance risk
  • Able to withstand the rigors of intensive treatment
  • Available for and compliant with adequate long-term follow-up

PRIOR CONCURRENT THERAPY:

  • No prior definitive surgery or radiotherapy for this malignancy
  • No prior chemotherapy, immunotherapy, or epidermal growth factor receptor inhibitors for any disease Patients who have had previous definitive surgery, or radiation therapy for this malignancy, and patients who have had any previous chemotherapy, immunotherapy, or EGF receptor inhibition for any disease are ineligible.

Exclusion Criteria Patients with primary cancers of the nasopharynx, paranasal sinus or salivary gland are ineligible.

Patients with unstable or uncontrolled angina, clinically apparent jaundice, or active infection are ineligible.

Patients with a history of any other malignancy (except squamous or basal cell skin cancer or cervical carcinoma in-situ) are ineligible, unless the patient has been continuously disease-free for at least 5 years.

Patients with any histologic diagnosis other than squamous cell carcinoma are ineligible.

Patients who might be a poor-compliance risk are ineligible.

Pregnant or breastfeeding women are ineligible. Women/men of reproductive potential must be willing to practice acceptable methods of birth control to prevent pregnancy.

  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: NCT00608205

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: David J. Adelstein, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Principal Investigator: Panayiotis Savvides, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00608205     History of Changes
Other Study ID Numbers: CASE3307, P30CA043703, NCI-2010-01197
Study First Received: January 30, 2008
Results First Received: July 11, 2013
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
stage III squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the larynx

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cisplatin
Fluorouracil
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

ClinicalTrials.gov processed this record on July 26, 2014