Clinical trial NCT00608205: Radiation Therapy Cisplatin With or Without Fluorouracil Patients With Stage III or Stage IV Head and Neck Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Head and Neck Cancer
Keywords: 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
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2008-02-06
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Relapse Free Survival
timeFrame: at 2 yrs from start of study
Secondary outcomes:
measure: Patterns of Failure
timeFrame: 2 years from start of study
measure: Overall Survival
timeFrame: 2 yrs from start of study
measure: Number of Patients With a Clinical Response-complete Disappearance of Detectable Tumor
timeFrame: at 12 weeks after completing chemoradiotherapy
measure: Number of Patients With a Pathological(Final)Complete Response
timeFrame: at 12 weeks after completing chemoradiotherapy and surgery
measure: Disease Recurrence
timeFrame: 2 years after start of study
measure: Number of Patients That Required a Feeding Tube
timeFrame: 12 weeks (after treatment)
measure: Number of Patients That Required a Feeding Tube
timeFrame: 8 months after start of treatment
measure: Number of Patients That Required a Feeding Tube
timeFrame: 12 months after start of treatment
measure: Number of Patients That Required a Feeding Tube
timeFrame: 24 months after start of treatment
measure: Nausea Level
timeFrame: 12 weeks (after treatment)
measure: Nausea Level
timeFrame: 8 months from start of treatment
measure: Nausea Level
timeFrame: 12 months from start of treatment
measure: Nausea Level
timeFrame: 24 months from start of treatment
measure: Dry Mouth
timeFrame: 12 weeks (after treatment)
measure: Dry Mouth
timeFrame: 8 months from start of treatment
measure: Dry Mouth
timeFrame: 12 months from start of treatment
measure: Dry Mouth
timeFrame: 24 months from start of treatment
measure: Pain
timeFrame: 12 weeks (after treatment)
measure: Pain
timeFrame: 8 months from start of treatment
measure: Pain
timeFrame: 12 months from start of treatment
measure: Pain
timeFrame: 24 months from start of treatment
measure: Quality of Life
timeFrame: 12 weeks (after treatment)
measure: Quality of Life
timeFrame: 8 months from start of treatment
measure: Quality of Life
timeFrame: 12 months from start of treatment
measure: Quality of Life
timeFrame: 24 months from start of treatment
measure: Eating
timeFrame: 12 weeks (after treatment)
measure: Eating
timeFrame: 8 months from start of treatment
measure: Eating
timeFrame: 12 months from start of treatment
measure: Eating
timeFrame: 24 months from start of treatment
measure: Swallowing
timeFrame: 12 weeks (after treatment)
measure: Swallowing
timeFrame: 8 months after start of treatment
measure: Swallowing
timeFrame: 12 months after start of treatment
measure: Swallowing
timeFrame: 24 months after start of treatment
measure: Alcohol Consumption
timeFrame: 12 weeks (after treatment)
measure: Alcohol Consumption
timeFrame: 8 months after start of treatment
measure: Alcohol Consumption
timeFrame: 12 months after start of treatment
measure: Alcohol Consumption
timeFrame: 24 months after start of treatment
measure: Solid Foods
timeFrame: 12 weeks (after treatment)
measure: Solid Foods
timeFrame: 8 months after start of treatment
measure: Solid Foods
timeFrame: 12 months after start of treatment
measure: Solid Foods
timeFrame: 24 months after start of treatment
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: David J. Adelstein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
name: Panayiotis Savvides, MD
role: PRINCIPAL_INVESTIGATOR
References: