Combination Chemotherapy and Radiation Therapy in Treating Patients With Stage III or Stage IV Head and Neck Cancer (Paradigm Trial) - Full Text View

Sponsors and Collaborators:	Dana-Farber Cancer Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00095875

Purpose

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.

Condition	Intervention	Phase
Head and Neck Cancer	Drug: carboplatin Drug: cisplatin Drug: docetaxel Drug: fluorouracil Radiation: radiation therapy	Phase III

MedlinePlus related topics: Cancer Head and Neck Cancer Radiation Therapy

Drug Information available for: Fluorouracil Cisplatin Carboplatin Docetaxel

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	A Randomized Phase III Comparing Sequential Therapy With TPF/Chemoradiation (ST) To Cisplatinum-Based Chemoradiotherapy [PARADIGM TRIAL]

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Survival at 3 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 [ Designated as safety issue: No ]
Response as assessed by RECIST criteria after completion of induction chemotherapy and chemoradiotherapy [ Designated as safety issue: No ]
Quality of life as assessed by longitudinal data analysis at baseline, 6 and 12 months, and then every 6 and 12 months for 5 years [ Designated as safety issue: No ]
Toxicity as assessed by the Chi-square or Fischer's exact test [ Designated as safety issue: Yes ]
Organ preservation rate as assessed by the Chi-square or Fischer's exact test [ Designated as safety issue: No ]

Estimated Enrollment:	330
Study Start Date:	August 2004
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental 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.	Drug: carboplatin Given IV Drug: cisplatin Given IV Drug: docetaxel Given IV Drug: fluorouracil Given IV Radiation: radiation therapy Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks
Arm II: Experimental Patients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks.	Drug: cisplatin Given IV Radiation: radiation therapy Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks

Arms

Assigned Interventions

Arm I: Experimental

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.

Drug: carboplatin

Given IV

Drug: cisplatin

Given IV

Drug: docetaxel

Given IV

Drug: fluorouracil

Given IV

Radiation: radiation therapy

Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks

Arm II: Experimental

Patients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks.

Drug: cisplatin

Given IV

Radiation: radiation therapy

Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks

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.

Eligibility

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00095875

Locations

United States, California
Rebecca and John Moores UCSD Cancer Center	Recruiting
La Jolla, California, United States, 92093-0658
Contact: Clinical Trials Office - Rebecca and John Moores UCSD Cancer 858-822-5354 cancercto@ucsd.edu
United States, Colorado
CCOP - Colorado Cancer Research Program	Recruiting
Denver, Colorado, United States, 80224
Contact: Patty Gibson 303-777-2663
United States, Florida
Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus	Recruiting
Boca Raton, Florida, United States, 33486
Contact: Clinical Trials Office - Eugene M. and Christine E. Lynn Cance 561-955-4800
United States, Georgia
Winship Cancer Institute of Emory University	Recruiting
Atlanta, Georgia, United States, 30322
Contact: Austin Hamilton 404-778-4150
United States, Illinois
Cardinal Bernardin Cancer Center at Loyola University Medical Center	Recruiting
Maywood, Illinois, United States, 60153
Contact: Clinical Trials Office - Cardinal Bernardin Cancer Center 708-226-4357
United States, Maine
Maine Center for Cancer Medicine and Blood Disorders - Scarborough	Recruiting
Scarborough, Maine, United States, 04074
Contact: Merideth Harriman 207-885-8587
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center	Recruiting
Baltimore, Maryland, United States, 21201
Contact: Clinical Trials Office - Greenebaum Cancer Center at Universit 800-888-8823
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Robert I. Haddad, MD 617-632-3090
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Jessica Ley 314-362-6963
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Recruiting
Lebanon, New Hampshire, United States, 03756-0002
Contact: Clinical Trials Office - Norris Cotton Cancer Center 603-650-7609 cancerhelp@dartmouth.edu
United States, New Jersey
UMDNJ University Hospital	Recruiting
Newark, New Jersey, United States, 07103
Contact: Lillian F. Pliner, MD, FACP 973-972-6257 plinerlf@umdnj.edu
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine	Recruiting
Bronx, New York, United States, 10461
Contact: Missak Haigentz, MD 718-920-4140 mhaigent@montefiore.org
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center	Recruiting
Charlotte, North Carolina, United States, 28232-2861
Contact: Clinical Trials Office - Blumenthal Cancer Center at Carolinas 704-355-2884
United States, Pennsylvania
UPMC Cancer Centers	Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Clinical Trials Office - UPMC Cancer Centers 412-647-8073
Germany
Klinikum der J.W. Goethe Universitaet	Recruiting
Frankfurt, Germany, D-60590
Contact: Contact Person 49-69-6301-4471

Sponsors and Collaborators

Dana-Farber Cancer Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Robert I. Haddad, MD

Dana-Farber Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute ( Robert I. Haddad )
Study ID Numbers:	CDR0000393548, DFCI-04006, AVENTIS-DFCI-04006
Study First Received:	November 9, 2004
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00095875 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Antimetabolites
Immunologic Factors
Laryngeal Carcinoma
Carboplatin
Squamous Cell Carcinoma
Immunosuppressive Agents
Carcinoma

Hypopharyngeal Cancer
Docetaxel
Cisplatin
Head and Neck Neoplasms
Fluorouracil
Epidermoid Carcinoma
Carcinoma, Squamous Cell

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Carboplatin

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Fluorouracil
Therapeutic Uses

ClinicalTrials.gov processed this record on May 07, 2009