Combination Chemotherapy and Radiation in Treating Patients With Stage III or IV Head and Neck Cancer (Paradigm Trial)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Robert I. Haddad, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00095875
First received: November 9, 2004
Last updated: October 25, 2013
Last verified: October 2013
  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
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III Comparing Sequential Therapy With TPF/Chemoradiation (ST) To Cisplatinum-Based Chemoradiotherapy [PARADIGM TRIAL]

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: 3-years ] [ Designated as safety issue: No ]
    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


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 [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 145
Study Start Date: August 2004
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: carboplatin
Given IV
Other Name: Paraplatin
Drug: cisplatin
Given IV
Other Name: Platinol
Drug: docetaxel
Given IV
Other Name: Taxotere
Drug: fluorouracil
Given IV
Other Name: Efudex
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.
Drug: cisplatin
Given IV
Other Name: Platinol

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
United States, Colorado
CCOP - Colorado Cancer Research Program
Denver, Colorado, United States, 80224
United States, Florida
Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
Boca Raton, Florida, United States, 33486
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Maine
Maine Center for Cancer Medicine and Blood Disorders - Scarborough
Scarborough, Maine, United States, 04074
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
United States, New Jersey
UMDNJ University Hospital
Newark, New Jersey, United States, 07103
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
United States, Pennsylvania
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
Germany
Klinikum der J.W. Goethe Universitaet
Frankfurt, Germany, D-60590
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Study Chair: Robert I. Haddad, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Publications:
Responsible Party: Robert I. Haddad, MD, Medical Oncology, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00095875     History of Changes
Obsolete Identifiers: NCT00705068
Other Study ID Numbers: DFCI 04-006, P30CA006516, CDR0000393548
Study First Received: November 9, 2004
Results First Received: May 15, 2013
Last Updated: October 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
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

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Docetaxel
Cisplatin
Carboplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 16, 2014