Clinical trial NCT00095875: Combination Chemotherapy and Radiation in Treating Patients With Stage III or IV Head and Neck Cancer (Paradigm Trial)
Official title: A Randomized Phase III Comparing Sequential Therapy With TPF/Chemoradiation (ST) To Cisplatinum-Based Chemoradiotherapy [PARADIGM TRIAL]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Head and Neck Cancer
Keywords: 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
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-11-09
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Overall Survival
timeFrame: 3-years
Secondary outcomes:
measure: 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
timeFrame: 5 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program
state: Colorado
city: Boca Raton
country: United States
facility: Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders - Scarborough
state: Maine
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Newark
country: United States
facility: UMDNJ University Hospital
state: New Jersey
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
state: New York
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
city: Frankfurt
country: Germany
facility: Klinikum der J.W. Goethe Universitaet
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Robert I. Haddad, MD
role: STUDY_CHAIR
References:
citation: Haddad R, O'Neill A, Rabinowits G, Tishler R, Khuri F, Adkins D, Clark J, Sarlis N, Lorch J, Beitler JJ, Limaye S, Riley S, Posner M. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 2013 Mar;14(3):257-64. doi: 10.1016/S1470-2045(13)70011-1. Epub 2013 Feb 13.