- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00095875
Combination Chemotherapy and Radiation in Treating Patients With Stage III or IV Head and Neck Cancer (Paradigm Trial)
A Randomized Phase III Comparing Sequential Therapy With TPF/Chemoradiation (ST) To Cisplatinum-Based Chemoradiotherapy [PARADIGM TRIAL]
RATIONALE: Drugs used in chemotherapy, such as docetaxel, cisplatin, fluorouracil, and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known which regimen of chemotherapy and radiation therapy is most effective in treating head and neck cancer.
PURPOSE: Randomized phase III trial to compare the effectiveness of two different regimens of chemotherapy and radiation therapy in treating patients who have stage III or stage IV head and neck cancer.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
OBJECTIVES:
Primary
- Compare 3-year survival of patients with previously untreated stage III or IV squamous cell carcinoma of the head and neck treated with induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil followed by radiotherapy and carboplatin or docetaxel vs radiotherapy and cisplatin only.
Secondary
- Compare 2-year progression-free status in patients treated with these regimens.
- Compare 5-year survival of patients treated with these regimens.
- Compare 3- and 5-year progression-free survival of patients treated with these regimens.
- Compare the complete response rate in patients treated with these regimens.
- Compare tumor site-specific survival in patients treated with these regimens.
- Compare functional organ preservation in patients treated with these regimens.
- Compare the toxicity of these regimens in these patients.
- Compare the quality of life of patients treated with these regimens.
- Correlate tissue and germline markers with response, local/regional control, and the development of distant metastases in patients treated with these regimens.
OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil. Treatment repeats every 21 days for 3 courses. Patients achieving a pathologic complete response at the primary site and a clinical complete response in the neck then receive carboplatin once weekly and undergo concurrent radiotherapy once daily, 5 days a week, for 7 weeks. Patients with a partial response at the primary site (i.e., positive biopsy), stable disease, or radiographic evidence of persistent disease in the neck receive docetaxel once weekly for 4 weeks and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks.
- Arm II: Patients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks.
Quality of life is assessed at baseline and then at 3, 12, and 24 months.
Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 330 patients will be accrued for this study.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Frankfurt, Germany, D-60590
- Klinikum der J.W. Goethe Universitaet
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California
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La Jolla, California, United States, 92093-0658
- Rebecca and John Moores UCSD Cancer Center
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Colorado
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Denver, Colorado, United States, 80224
- CCOP - Colorado Cancer Research Program
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Florida
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Boca Raton, Florida, United States, 33486
- Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
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Georgia
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Atlanta, Georgia, United States, 30322
- Winship Cancer Institute of Emory University
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Illinois
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Maywood, Illinois, United States, 60153
- Cardinal Bernardin Cancer Center at Loyola University Medical Center
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Maine
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Scarborough, Maine, United States, 04074
- Maine Center for Cancer Medicine and Blood Disorders - Scarborough
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Maryland
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Baltimore, Maryland, United States, 21201
- Greenebaum Cancer Center at University of Maryland Medical Center
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
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Missouri
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Saint Louis, Missouri, United States, 63110
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
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New Hampshire
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Lebanon, New Hampshire, United States, 03756-0002
- Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
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New Jersey
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Newark, New Jersey, United States, 07103
- UMDNJ University Hospital
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New York
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Bronx, New York, United States, 10461
- Albert Einstein Cancer Center at Albert Einstein College of Medicine
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North Carolina
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Charlotte, North Carolina, United States, 28232-2861
- Blumenthal Cancer Center at Carolinas Medical Center
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- UPMC Cancer Centers
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
List of Inclusion Criteria:
Histologically or cytologically confirmed squamous cell carcinoma of the head and neck
- Stage III or IV* disease
One of the following primary tumor sites:
Oral cavity
- No mandible invasion
- Oropharynx
- Hypopharynx
- Larynx
The following primary tumor sites are excluded:
- Nasal cavity
- Paranasal cavity
- Nasopharynx NOTE: *No evidence of distant metastases by chest x-ray, abdominal ultrasound, or CT scan (for patients with liver function test abnormalities) or bone scan (for patients with local symptoms)
- At least 1 uni- or bi-dimensionally measurable lesion
PATIENT CHARACTERISTICS:
Age
- Over 18
Performance status
- WHO 0-1
Life expectancy
- Not specified
Hematopoietic
- Neutrophil count > 1,500/mm^3
- Platelet count > 100,000/mm^3
- Hemoglobin > 10 g/dL
Hepatic
- Bilirubin normal
- AST or ALT within eligibility range
- Alkaline phosphatase within eligibility range
Renal
- Creatinine clearance > 60 mL/min
Cardiovascular
- No unstable cardiac disease despite treatment
- No myocardial infarction within the past 6 months
Pulmonary
No chronic obstructive pulmonary disease, defined as requiring hospitalization for pneumonia or respiratory decompensation within the past year
- Obstruction caused by the tumor allowed
Neurologic
- No symptomatic peripheral neuropathy > grade 2
- No symptomatic altered hearing > grade 2
- No history of significant neurologic or psychiatric disorders, including dementia or seizures
Other
- No active drug addiction, including alcohol, cocaine, or intravenous drugs within the past 6 months
- No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, or other cancer curatively treated by surgery alone
- No active, clinically significant, uncontrolled infection
- No autoimmune disease requiring therapy
- No unhealed or clinically active peptic ulcer disease
- No hypercalcemia
- No other serious illness or medical condition
- No involuntary weight loss > 25% of body weight within the past 2 months
- HIV negative
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 3 months after study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No prior chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- No prior radiotherapy
Surgery
- No prior organ transplantation
No prior surgery for this cancer
- Biopsy allowed
Other
- More than 30 days since prior participation in another investigational study
- No other concurrent anticancer therapy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Arm I
Patients receive induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil.
Treatment repeats every 21 days for 3 courses.
Patients achieving a pathologic complete response at the primary site and a clinical complete response in the neck then receive carboplatin once weekly and undergo concurrent radiotherapy once daily, 5 days a week, for 7 weeks.
Patients with a partial response at the primary site (i.e., positive biopsy), stable disease, or radiographic evidence of persistent disease in the neck receive docetaxel once weekly for 4 weeks and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks.
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Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
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Experimental: Arm II
Patients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks.
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Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: 3-years
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To compare the 3-year survival achieved by docetaxel/cisplatin/5-FU based sequential therapy with platinum based chemo radiotherapy in patients with locally advanced SCCHN.
Overall survival is defined as the time from date of randomisation to death from any cause.
Patients alive at the time of current analysis were censored at the date last known to be alive.Kaplan-Meier method was used to estimate overall survival
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3-years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival and Disease-specific Survival as Assessed by Disease Progression or Death and Log Rank Tests at the Median, and 2, 3, and 5 Years
Time Frame: 5 years
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Progression free survival was defined as the time from date of randomisation to disease progression or death from any cause without progression whichever occurred first; otherwise, patients were censored at the date last known to be free of progression.
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5 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Robert I. Haddad, MD, Dana-Farber Cancer Institute
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- 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
- 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
Additional Relevant MeSH Terms
- Neoplasms
- Neoplasms by Site
- Head and Neck Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Docetaxel
- Carboplatin
- Fluorouracil
Other Study ID Numbers
- DFCI 04-006
- P30CA006516 (U.S. NIH Grant/Contract)
- CDR0000393548 (Registry Identifier: NCI PDQ)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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