A Randomized Phase III Comparing Sequential Therapy With TPF/Chemoradiation (ST) To Cisplatinum-Based Chemoradiotherapy [PARADIGM TRIAL]
18 Years
N/A
Both
Head and Neck Cancer
Trial Information
A Randomized Phase III Comparing Sequential Therapy With TPF/Chemoradiation (ST) To Cisplatinum-Based Chemoradiotherapy [PARADIGM TRIAL]
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Survival
Outcome Description:
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
Outcome Time Frame:
3-years
Safety Issue:
No
Principal Investigator
Robert I. Haddad, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Dana-Farber Cancer Institute
Authority:
United States: Institutional Review Board
Study ID:
DFCI 04-006
NCT ID:
NCT00095875
Start Date:
August 2004
Completion Date:
Related Keywords:
- Head and Neck Cancer
- stage III squamous cell carcinoma of the hypopharynx
- stage III squamous cell carcinoma of the larynx
- stage III squamous cell carcinoma of the lip and oral cavity
- stage III squamous cell carcinoma of the oropharynx
- stage IV squamous cell carcinoma of the hypopharynx
- stage IV squamous cell carcinoma of the larynx
- stage IV squamous cell carcinoma of the lip and oral cavity
- stage IV squamous cell carcinoma of the oropharynx
- Head and Neck Neoplasms
Name | Location |
|---|---|
| Cardinal Bernardin Cancer Center at Loyola University Medical Center | Maywood, Illinois 60153-5500 |
| CCOP - Colorado Cancer Research Program | Denver, Colorado 80224-2522 |
| Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center | Lebanon, New Hampshire 03756-0002 |
| Rebecca and John Moores UCSD Cancer Center | La Jolla, California 92093-0658 |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
| Maine Center for Cancer Medicine and Blood Disorders - Scarborough | Scarborough, Maine 04074 |
| Blumenthal Cancer Center at Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
| UMDNJ University Hospital | Newark, New Jersey 07103 |
| Winship Cancer Institute of Emory University | Atlanta, Georgia 30322 |
| Albert Einstein Cancer Center at Albert Einstein College of Medicine | Bronx, New York 10461 |
| Greenebaum Cancer Center at University of Maryland Medical Center | Baltimore, Maryland 21201 |
| Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis | St. Louis, Missouri 63110 |
| UPMC Cancer Centers | Pittsburgh, Pennsylvania 15232 |
| Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus | Boca Raton, Florida 33486 |
