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

• ClinicalTrials.gov Identifier: NCT00095875
• Recruitment Status: Completed
• First Posted: November 9, 2004
• Results First Posted: July 2, 2013
• Last Update Posted: November 19, 2013
• Sponsor: Dana-Farber Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Robert I. Haddad, MD, Dana-Farber Cancer Institute

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Head and Neck Cancer
• Interventions: Drug: carboplatin; Drug: cisplatin; Drug: docetaxel; Drug: fluorouracil
• Enrollment: 145

Participant Flow

Recruitment Details	Between August 24, 2004 and December 29, 2008 145 patients were enrolled across 16 sites.
Pre-assignment Details	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.

Arm/Group Title	Arm I	Arm II
Arm/Group 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. 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	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
Period Title: Overall Study
Started	70	75
Completed	56	66
Not Completed	14	9

Baseline Characteristics

Arm/Group Title		Arm I	Arm II	Total
Arm/Group 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. 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	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 of all reporting groups
Overall Number of Baseline Participants		70	75	145
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	70 participants	75 participants	145 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	59 84.3%	66 88.0%	125 86.2%
	>=65 years	11 15.7%	9 12.0%	20 13.8%
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	70 participants	75 participants	145 participants
		55 (9)	54 (8)	55 (8.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	70 participants	75 participants	145 participants
	Female	6 8.6%	12 16.0%	18 12.4%
	Male	64 91.4%	63 84.0%	127 87.6%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	70 participants	75 participants	145 participants
United States		69	69	138
Germany		1	6	7

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I	Arm II
Arm/Group 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. 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	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 Number of Participants Analyzed	70	75
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percent of patients
	73; (60 to 82)	78; (66 to 86)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I	Arm II
Arm/Group 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. 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	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 Number of Participants Analyzed	70	75
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percent of patients
	67; (54 to 76)	69; (56 to 79)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	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.
Arm/Group Title	Arm I	Arm II
Arm/Group 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. 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	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
All-Cause Mortality
	Arm I	Arm II
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Arm I	Arm II
	Affected / at Risk (%)	Affected / at Risk (%)
Total	56/70 (80.00%)	29/75 (38.67%)
Blood and lymphatic system disorders
Febrile Neutropenia	16/70 (22.86%)	1/75 (1.33%)
Gastrointestinal disorders
Mucositis	33/70 (47.14%)	12/75 (16.00%)
Xerostomia	5/70 (7.14%)	5/75 (6.67%)
General disorders
Pain	2/70 (2.86%)	9/75 (12.00%)
Nervous system disorders
Neurpathy	0/70 (0.00%)	2/75 (2.67%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm I	Arm II
	Affected / at Risk (%)	Affected / at Risk (%)
Total	70/70 (100.00%)	75/75 (100.00%)
Gastrointestinal disorders
Mucositis	29/70 (41.43%)	44/75 (58.67%)
Xerostomia	42/70 (60.00%)	46/75 (61.33%)
General disorders
Pain	41/70 (58.57%)	35/75 (46.67%)
Immune system disorders
Neuropathy	22/70 (31.43%)	18/75 (24.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Robert I Haddad, MD
• Organization: Dana Farber Cancer Institute
• Phone: 617-632-3090
• EMail: rihaddad@partners.org

Publications of Results:

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.

• Responsible Party: Robert I. Haddad, MD, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00095875
• Obsolete Identifiers: NCT00705068
• Other Study ID Numbers: DFCI 04-006; P30CA006516 ( U.S. NIH Grant/Contract ); CDR0000393548 ( Registry Identifier: NCI PDQ )
• First Submitted: November 9, 2004
• First Posted: November 9, 2004
• Results First Submitted: May 15, 2013
• Results First Posted: July 2, 2013
• Last Update Posted: November 19, 2013