Trial Outcomes & Findings for Combination Chemotherapy and Radiation in Treating Patients With Stage III or IV Head and Neck Cancer (Paradigm Trial) (NCT NCT00095875)

Last Updated: 2013-11-19

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

145 participants

Primary outcome timeframe

3-years

Results posted on

2013-11-19

Participant Flow

Between August 24, 2004 and December 29, 2008 145 patients were enrolled across 16 sites.

Patients were randomly assigned in a 1:1 ratio to recieve either induction chemotherapy with 3 cycles of TPF followed by concurrent chemoradiotherapy with either docetaxel or carboplatin or concurrent chemoradiotherapy alone with 2 cycles of bolus cisplatin.

Participant milestones

Participant milestones
Measure	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. cisplatin : Given IV radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks carboplatin : Given IV fluorouracil : Given IV docetaxel : 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. cisplatin : Given IV radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks
Overall Study STARTED	70	75
Overall Study COMPLETED	56	66
Overall Study NOT COMPLETED	14	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I n=70 Participants 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. cisplatin : Given IV radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks carboplatin : Given IV fluorouracil : Given IV docetaxel : Given IV	Arm II n=75 Participants Patients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks. cisplatin : Given IV radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks	Total n=145 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	59 Participants n=93 Participants	66 Participants n=4 Participants	125 Participants n=27 Participants
Age, Categorical >=65 years	11 Participants n=93 Participants	9 Participants n=4 Participants	20 Participants n=27 Participants
Age Continuous	55 years STANDARD_DEVIATION 9 • n=93 Participants	54 years STANDARD_DEVIATION 8 • n=4 Participants	55 years STANDARD_DEVIATION 8.4 • n=27 Participants
Sex: Female, Male Female	6 Participants n=93 Participants	12 Participants n=4 Participants	18 Participants n=27 Participants
Sex: Female, Male Male	64 Participants n=93 Participants	63 Participants n=4 Participants	127 Participants n=27 Participants
Region of Enrollment United States	69 participants n=93 Participants	69 participants n=4 Participants	138 participants n=27 Participants
Region of Enrollment Germany	1 participants n=93 Participants	6 participants n=4 Participants	7 participants n=27 Participants

PRIMARY outcome

Timeframe: 3-years

Outcome measures

Outcome measures
Measure	Arm I n=70 Participants 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. cisplatin : Given IV radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks carboplatin : Given IV fluorouracil : Given IV docetaxel : Given IV	Arm II n=75 Participants Patients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks. cisplatin : Given IV radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks
Overall Survival	73 percent of patients Interval 60.0 to 82.0	78 percent of patients Interval 66.0 to 86.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm I n=70 Participants 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. cisplatin : Given IV radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks carboplatin : Given IV fluorouracil : Given IV docetaxel : Given IV	Arm II n=75 Participants Patients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks. cisplatin : Given IV radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks
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	67 percent of patients Interval 54.0 to 76.0	69 percent of patients Interval 56.0 to 79.0

Adverse Events

Arm I

Serious events: 56 serious events

Other events: 70 other events

Deaths: 0 deaths

Arm II

Serious events: 29 serious events

Other events: 75 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm I n=70 participants at risk 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. cisplatin : Given IV radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks carboplatin : Given IV fluorouracil : Given IV docetaxel : Given IV	Arm II n=75 participants at risk Patients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks. cisplatin : Given IV radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks
Gastrointestinal disorders Mucositis	47.1% 33/70 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.	16.0% 12/75 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.
Blood and lymphatic system disorders Febrile Neutropenia	22.9% 16/70 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.	1.3% 1/75 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.
General disorders Pain	2.9% 2/70 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.	12.0% 9/75 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.
Gastrointestinal disorders Xerostomia	7.1% 5/70 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.	6.7% 5/75 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.
Nervous system disorders Neurpathy	0.00% 0/70 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.	2.7% 2/75 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.

Other adverse events

Other adverse events
Measure	Arm I n=70 participants at risk 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. cisplatin : Given IV radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks carboplatin : Given IV fluorouracil : Given IV docetaxel : Given IV	Arm II n=75 participants at risk Patients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks. cisplatin : Given IV radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks
Gastrointestinal disorders Mucositis	41.4% 29/70 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.	58.7% 44/75 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.
General disorders Pain	58.6% 41/70 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.	46.7% 35/75 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.
Gastrointestinal disorders Xerostomia	60.0% 42/70 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.	61.3% 46/75 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.
Immune system disorders Neuropathy	31.4% 22/70 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.	24.0% 18/75 Only the following adverse events were records: mucositis, febrile neutropenia, pain, xerostomia, feeding tube placement, and neuropathy which was deemed pertinent to the comparision of regimens in this setting.

Additional Information

Robert I Haddad, MD

Dana Farber Cancer Institute

Phone: 617-632-3090

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place