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A Randomized Phase III Comparing Sequential Therapy With TPF/Chemoradiation (ST) To Cisplatinum-Based Chemoradiotherapy [PARADIGM TRIAL]


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Head and Neck Cancer

Thank you

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 CenterMaywood, Illinois  60153-5500
CCOP - Colorado Cancer Research ProgramDenver, Colorado  80224-2522
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756-0002
Rebecca and John Moores UCSD Cancer CenterLa Jolla, California  92093-0658
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
Maine Center for Cancer Medicine and Blood Disorders - ScarboroughScarborough, Maine  04074
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
UMDNJ University HospitalNewark, New Jersey  07103
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322
Albert Einstein Cancer Center at Albert Einstein College of MedicineBronx, New York  10461
Greenebaum Cancer Center at University of Maryland Medical CenterBaltimore, Maryland  21201
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
UPMC Cancer CentersPittsburgh, Pennsylvania  15232
Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main CampusBoca Raton, Florida  33486