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

Head and Neck Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00095875
• Other study ID #: DFCI 04-006
• Secondary ID: P30CA006516CDR00
• Status: Completed
• Phase: Phase 3
• First received: November 9, 2004
• Last updated: October 25, 2013
• Start date: August 2004
• Est. completion date: April 2012

Study information

• Verified date: October 2013
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00705068

Recruitment information / eligibility

• Status: Completed
• Enrollment: 145
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• carboplatin
Given IV
• cisplatin
Given IV
• docetaxel
Given IV
• fluorouracil
Given IV

Locations

Country	Name	City	State
Germany	Klinikum der J.W. Goethe Universitaet	Frankfurt
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus	Boca Raton	Florida
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	CCOP - Colorado Cancer Research Program	Denver	Colorado
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	UMDNJ University Hospital	Newark	New Jersey
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	Maine Center for Cancer Medicine and Blood Disorders - Scarborough	Scarborough	Maine

Sponsors (2)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Germany, 

References & Publications (1)

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 chemorad — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	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	3-years	No
Secondary	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	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.	5 years	No