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

Primary Purpose

Head and Neck Cancer

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
carboplatin
cisplatin
docetaxel
fluorouracil
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rebecca and John Moores UCSD Cancer Center
  • CCOP - Colorado Cancer Research Program
  • Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
  • Winship Cancer Institute of Emory University
  • Cardinal Bernardin Cancer Center at Loyola University Medical Center
  • Maine Center for Cancer Medicine and Blood Disorders - Scarborough
  • Greenebaum Cancer Center at University of Maryland Medical Center
  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
  • UMDNJ University Hospital
  • Albert Einstein Cancer Center at Albert Einstein College of Medicine
  • Blumenthal Cancer Center at Carolinas Medical Center
  • UPMC Cancer Centers
  • Klinikum der J.W. Goethe Universitaet

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I

Arm II

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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

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
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.

Full Information

First Posted
November 9, 2004
Last Updated
October 25, 2013
Sponsor
Dana-Farber Cancer Institute
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00095875
Brief Title
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

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
August 2004 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
145 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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 Title
Arm II
Arm Type
Experimental
Arm Description
Patients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
carboplatin
Other Intervention Name(s)
Paraplatin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
Platinol
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
docetaxel
Other Intervention Name(s)
Taxotere
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Other Intervention Name(s)
Efudex
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Overall Survival
Description
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
Time Frame
3-years
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert I. Haddad, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Rebecca and John Moores UCSD Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
CCOP - Colorado Cancer Research Program
City
Denver
State/Province
Colorado
ZIP/Postal Code
80224
Country
United States
Facility Name
Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
Winship Cancer Institute of Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Cardinal Bernardin Cancer Center at Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Maine Center for Cancer Medicine and Blood Disorders - Scarborough
City
Scarborough
State/Province
Maine
ZIP/Postal Code
04074
Country
United States
Facility Name
Greenebaum Cancer Center at University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756-0002
Country
United States
Facility Name
UMDNJ University Hospital
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
Albert Einstein Cancer Center at Albert Einstein College of Medicine
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Blumenthal Cancer Center at Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28232-2861
Country
United States
Facility Name
UPMC Cancer Centers
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Klinikum der J.W. Goethe Universitaet
City
Frankfurt
ZIP/Postal Code
D-60590
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
23414589
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.
Results Reference
result

Learn more about this trial

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

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