Head and Neck CancerPhase 3NCT00095875
Combination Chemotherapy and Radiation in Treating Patients With Stage III or IV Head and Neck Cancer (Paradigm Trial)
A Phase 3 study testing carboplatin, cisplatin and docetaxel in people with Head and Neck Cancer, run by Dana-Farber Cancer Institute at 15 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- carboplatin, cisplatin and docetaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 145 participants
- Where
- 15 sitesin 2 countries
- Study dates
- Aug 2004to Apr 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
United States14 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, 21201
Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
Boca Raton, Florida, 33486
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, 28232-2861
CCOP - Colorado Cancer Research Program
Denver, Colorado, 80224
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, 92093-0658
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756-0002
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, 60153
UMDNJ University Hospital
Newark, New Jersey, 07103
UPMC Cancer Centers
Pittsburgh, Pennsylvania, 15232
Maine Center for Cancer Medicine and Blood Disorders - Scarborough
Scarborough, Maine, 04074
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St Louis, Missouri, 63110
Albert Einstein Cancer Center at Albert Einstein College of Medicine
The Bronx, New York, 10461
About this study
Official title: A Randomized Phase III Comparing Sequential Therapy With TPF/Chemoradiation (ST) To Cisplatinum-Based Chemoradiotherapy [PARADIGM TRIAL]
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.
Read the 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
- Being tested
- carboplatin, cisplatin, docetaxel, fluorouracil
- 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
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
carboplatinDrug
Also called Paraplatin
Given IV
cisplatinDrug
Also called Platinol
Given IV
docetaxelDrug
Also called Taxotere
Given IV
fluorouracilDrug
Also called Efudex
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | 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. Receives: Drug: carboplatin; Drug: cisplatin; Drug: docetaxel; Drug: fluorouracil |
| Arm II | Experimental | Patients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks. Receives: Drug: cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3-years
Secondary outcomes (1)
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.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2004 (estimated)
- Study startAug 2004
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 145 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Robert I. Haddad, MD, Dana-Farber Cancer Institute
- Investigators
- Robert I. Haddad, MD, Study chair, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00095875
- Sponsor's protocol ID
- DFCI 04-006
- Other IDs
- P30CA006516, CDR0000393548
- Status last verified
- Oct 2013
- First submitted
- 9 Nov 2004
- Last updated
- 19 Nov 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 23414589
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase III Comparing Sequential Therapy With TPF/Chemoradiation (ST) To Cisplatinum-Based Chemoradiotherapy [PARADIGM TRIAL]
- ClinicalTrials.gov ID
- NCT00095875
- Acronym / sponsor ID
- DFCI 04-006
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 145 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Aug 2004
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 9 Nov 2004 (estimated)
- Results
- Posted 2 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: carboplatin, Drug: cisplatin, Drug: docetaxel, Drug: fluorouracilPatients 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 | Experimental | Drug: cisplatinPatients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| carboplatinAlso: ParaplatinGiven IV | Drug | Arm I |
| cisplatinAlso: PlatinolGiven IV | Drug | Arm I, Arm II |
| docetaxelAlso: TaxotereGiven IV | Drug | Arm I |
| fluorouracilAlso: EfudexGiven IV | Drug | Arm I |
Primary outcome
Overall Survival
Time frame: 3-years
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
1 secondary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23414589Haddad 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert I. Haddad, MD study chair
Dana-Farber Cancer Institute
15 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing carboplatin, cisplatin and docetaxel in people with Head and Neck Cancer, run by Dana-Farber Cancer Institute at 15 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 3-years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00095875, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2013.