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

NCT ID: NCT00095875

Last Updated: 2013-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-08-31
• Study Completion Date: 2012-04-30

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

Given IV

cisplatin

Intervention Type: DRUG

Given IV

docetaxel

Intervention Type: DRUG

Given IV

fluorouracil

Intervention Type: DRUG

Given IV

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.

Group Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

Given IV

Interventions

carboplatin

Given IV

Intervention Type: DRUG

cisplatin

Given IV

Intervention Type: DRUG

docetaxel

Given IV

Intervention Type: DRUG

fluorouracil

Given IV

Intervention Type: DRUG

Other Intervention Names

Paraplatin; Platinol; Taxotere; Efudex

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Robert I. Haddad, MD

Medical Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert I. Haddad, MD

Role: STUDY_CHAIR

Dana-Farber Cancer Institute

Locations

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States

CCOP - Colorado Cancer Research Program

Denver, Colorado, United States

Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus

Boca Raton, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, United States

Maine Center for Cancer Medicine and Blood Disorders - Scarborough

Scarborough, Maine, United States

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

UMDNJ University Hospital

Newark, New Jersey, United States

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, United States

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States

Klinikum der J.W. Goethe Universitaet

Frankfurt, , Germany

Countries

United States; Germany

References

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.

Reference Type: RESULT

PMID: 23414589 (View on PubMed)

Other Identifiers

P30CA006516

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000393548

Identifier Type: REGISTRY

Identifier Source: secondary_id

DFCI 04-006

Identifier Type: -

Identifier Source: org_study_id

NCT00705068

Identifier Type: -

Identifier Source: nct_alias