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Reduced-Dose Intensity-Modulated Radiation Therapy With or Without Cisplatin in Treating Patients With Advanced Oropharyngeal Cancer

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ClinicalTrials.gov Identifier: NCT02254278
Recruitment Status : Active, not recruiting
First Posted : October 1, 2014
Results First Posted : August 12, 2020
Last Update Posted : January 22, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Stage III Oropharyngeal Squamous Cell Carcinoma
Stage IVA Oropharyngeal Squamous Cell Carcinoma
Stage IVB Oropharyngeal Squamous Cell Carcinoma
Stage IVC Oropharyngeal Squamous Cell Carcinoma
Tongue Carcinoma
Interventions Drug: Cisplatin
Radiation: IMRT 6 weeks
Radiation: IMRT 5 weeks
Enrollment 316
Recruitment Details  
Pre-assignment Details After first step registration and prior to randomization, patients were tested for p16. Only patients with p16-positive tumors continued on to randomization. In total, 316 patients were enrolled and 308 were randomized.
Arm/Group Title IMRT 6 Weeks + Cisplatin IMRT 5 Weeks
Hide Arm/Group Description

Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks

IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

IMRT 5 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy
Period Title: Overall Study
Started 158 150
Eligible 157 149
Started Study Treatment [1] 152 147
Negative Post-treatment PET [2] 58 57
Completed [3] 157 149
Not Completed 1 1
Reason Not Completed
Protocol Violation             1             1
[1]
Randomized and eligible participants who started study treatment
[2]
Randomized and eligible with negative post-treatment positron emission tomography (PET) scan
[3]
Participants contributing data to results are considered to have completed the study
Arm/Group Title IMRT 6 Weeks + Cisplatin IMRT 5 Weeks Total
Hide Arm/Group Description

Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks

IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

IMRT 5 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy Total of all reporting groups
Overall Number of Baseline Participants 157 149 306
Hide Baseline Analysis Population Description
Randomized and eligible patients
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 149 participants 306 participants
≤ 49
28
  17.8%
14
   9.4%
42
  13.7%
50 - 59
56
  35.7%
60
  40.3%
116
  37.9%
60 - 69
46
  29.3%
55
  36.9%
101
  33.0%
≥ 70
27
  17.2%
20
  13.4%
47
  15.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 149 participants 306 participants
Female
24
  15.3%
25
  16.8%
49
  16.0%
Male
133
  84.7%
124
  83.2%
257
  84.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 149 participants 306 participants
Hispanic or Latino
3
   1.9%
7
   4.7%
10
   3.3%
Not Hispanic or Latino
143
  91.1%
130
  87.2%
273
  89.2%
Unknown or Not Reported
11
   7.0%
12
   8.1%
23
   7.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 149 participants 306 participants
American Indian or Alaska Native
1
   0.6%
1
   0.7%
2
   0.7%
Asian
0
   0.0%
4
   2.7%
4
   1.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   0.6%
2
   1.3%
3
   1.0%
White
151
  96.2%
130
  87.2%
281
  91.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
4
   2.5%
12
   8.1%
16
   5.2%
Zubrod performance status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 149 participants 306 participants
0: Asymptomatic
132
  84.1%
113
  75.8%
245
  80.1%
1: Symptomatic but completely ambulatory
25
  15.9%
36
  24.2%
61
  19.9%
Smoking history (pack years)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 149 participants 306 participants
0
112
  71.3%
101
  67.8%
213
  69.6%
>0 - <5
26
  16.6%
32
  21.5%
58
  19.0%
5 - 10
19
  12.1%
16
  10.7%
35
  11.4%
[1]
Measure Description: Smoking history as measured in pack-years, calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked.
Primary tumor site  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 149 participants 306 participants
Oropharynx NOS (not otherwise specified)
4
   2.5%
13
   8.7%
17
   5.6%
Tonsillar fossa, tonsil
83
  52.9%
78
  52.3%
161
  52.6%
Base of tongue
68
  43.3%
58
  38.9%
126
  41.2%
Pharyngeal oropharynx
1
   0.6%
0
   0.0%
1
   0.3%
Posterior pharyngeal wall
1
   0.6%
0
   0.0%
1
   0.3%
T stage, clinical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 149 participants 306 participants
T1
64
  40.8%
51
  34.2%
115
  37.6%
T2
67
  42.7%
80
  53.7%
147
  48.0%
T3
26
  16.6%
18
  12.1%
44
  14.4%
[1]
Measure Description: Tumor stage per the American Joint Committee on Cancer (AJCC) 7th ed. refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b.
N stage, clinical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 149 participants 306 participants
N0
6
   3.8%
7
   4.7%
13
   4.2%
N1
28
  17.8%
34
  22.8%
62
  20.3%
N2a
24
  15.3%
19
  12.8%
43
  14.1%
N2b
99
  63.1%
89
  59.7%
188
  61.4%
[1]
Measure Description: Regional lymph nodes staging per American Joint Committee on Cancer (AJCC) 7th ed. refers to the number and/or extent of spread of lymph nodes that contain cancer. The higher the number after the N, the greater the involvement of regional lymph nodes.
Radiation Therapy (RT) planning (as stratified)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 149 participants 306 participants
Unilateral
52
  33.1%
47
  31.5%
99
  32.4%
Bilateral
105
  66.9%
102
  68.5%
207
  67.6%
[1]
Measure Description: Radiation therapy plan included unilateral or bilateral radiation to the neck, as provided by the treating site at stratification.
RT planning (per central review)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 149 participants 306 participants
Unilateral
16
  10.2%
21
  14.1%
37
  12.1%
Bilateral
136
  86.6%
125
  83.9%
261
  85.3%
Unknown
5
   3.2%
3
   2.0%
8
   2.6%
[1]
Measure Description: Radiation therapy plan included unilateral or bilateral radiation to the neck, as provided by central review by the study radiation oncologist.
1.Primary Outcome
Title Percentage of Participants Alive Without Progression at Two Years (Progression-free Survival)
Hide Description Progression is defined as local, regional, or distant disease progression or death due to any cause. Percentage is estimated using the binomial distribution.
Time Frame From randomization to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Two-year data was available for 147/157 (Arm 1) and 145/149 (Arm 2) randomized and eligible participants.
Arm/Group Title IMRT 6 Weeks + Cisplatin (Arm 1) IMRT 5 Weeks (Arm 2)
Hide Arm/Group Description:

Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks

IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

IMRT 5 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy
Overall Number of Participants Analyzed 147 145
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
90.5 [1] 
(86.6 to NA)
87.6 [1] 
(83.3 to NA)
[1]
one-side confidence interval
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IMRT 6 Weeks + Cisplatin (Arm 1)
Comments Assuming a binomial distribution, 140 eligible patients per arm were required for 80% power and 1-sided type I error rate of 10% to test the null hypothesis of 2-year progression-free survival (PFS) rate ≤ 85% against the alternative hypothesis of > 85% with a binomial test. The arms are not compared to each other; they are each tested separately against the null hypothesis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method binomial
Comments One-sided significance level=0.10
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection IMRT 5 Weeks (Arm 2)
Comments Assuming a binomial distribution, 140 eligible patients per arm were required for 80% power and 1-sided type I error rate of 10% to test the null hypothesis of 2-year PFS rate ≤ 85% against the alternative hypothesis of > 85% with a binomial test. The arms are not compared to each other; they are each tested separately against the null hypothesis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23
Comments [Not Specified]
Method bionmial
Comments One-sided significance level = 0.10
2.Secondary Outcome
Title Percentage of Participants With Local-regional Failure
Hide Description Local-regional failure is defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown > 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression. Distant metastasis and death due to other causes are considered competing risks. Local-regional failure time is defined as time from randomization to the date of first progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method.
Time Frame From randomization to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and eligible participants
Arm/Group Title IMRT 6 Weeks + Cisplatin IMRT 5 Weeks
Hide Arm/Group Description:

Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks

IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

IMRT 5 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy
Overall Number of Participants Analyzed 157 149
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Six months
0.7
(0.1 to 3.3)
2.0
(0.6 to 5.4)
Two years
3.3
(1.2 to 7.1)
9.5
(5.5 to 15.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IMRT 6 Weeks + Cisplatin, IMRT 5 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Log Rank
Comments Two-sided significance level = 0.05
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.17 to 0.90
Estimation Comments Reference level = IMRT 5 weeks
3.Secondary Outcome
Title Percentage of Participants With Distant Metastasis
Hide Description Distant metastasis is defined as distant progression. Local-regional failure and death due to any cause are considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method.
Time Frame From randomization to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and eligible participants
Arm/Group Title IMRT 6 Weeks + Cisplatin IMRT 5 Weeks
Hide Arm/Group Description:

Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks

IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

IMRT 5 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy
Overall Number of Participants Analyzed 157 149
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Six months
0
(0 to 0)
0
(0 to 0)
Two years
4.0
(1.6 to 8.0)
2.1
(0.6 to 5.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IMRT 6 Weeks + Cisplatin, IMRT 5 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments [Not Specified]
Method Log Rank
Comments Two-sided significance level = 0.05
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.43
Confidence Interval (2-Sided) 95%
0.4 to 5.08
Estimation Comments Reference level = IMRT 5 weeks
4.Secondary Outcome
Title Percentage of Participants Alive
Hide Description Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.
Time Frame from randomization to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and eligible participants
Arm/Group Title IMRT 6 Weeks + Cisplatin IMRT 5 Weeks
Hide Arm/Group Description:

Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks

IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

IMRT 5 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy
Overall Number of Participants Analyzed 157 149
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Six months
99.3
(98.1 to 100)
98.0
(95.7 to 100)
Two years
96.7
(93.9 to 99.5)
97.3
(94.6 to 99.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IMRT 6 Weeks + Cisplatin, IMRT 5 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.93
Comments Two-side significance level = 0.05
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.31 to 2.95
Estimation Comments Reference level = IMRT 5 weeks
5.Secondary Outcome
Title Percentage of Participants With Grade 3+ Adverse Events
Hide Description Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.
Time Frame End of radiation therapy (RT) (approximately 6 weeks for Arm 1 and 5 weeks for Arm 2), then 1 month, 6 months, 1 year, and two years after end of RT
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and eligible participants who started study treatment. Adverse event data was not available for all participants at each time point.
Arm/Group Title IMRT 6 Weeks + Cisplatin (Arm 1) IMRT 5 Weeks (Arm 2)
Hide Arm/Group Description:

Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks

IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

IMRT 5 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy
Overall Number of Participants Analyzed 152 147
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
End of RT Number Analyzed 152 participants 147 participants
73.7
(65.9 to 80.5)
46.3
(38.0 to 54.7)
1 month post-RT Number Analyzed 144 participants 142 participants
36.1
(28.3 to 44.5)
28.2
(21.0 to 36.3)
6 months post-RT Number Analyzed 140 participants 126 participants
17.9
(11.9 to 25.2)
11.1
(6.2 to 17.9)
1 year post-RT Number Analyzed 143 participants 134 participants
14.0
(8.8 to 20.8)
9.0
(4.7 to 15.1)
2 years post-RT Number Analyzed 128 participants 122 participants
8.6
(4.4 to 14.9)
7.4
(3.4 to 13.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IMRT 6 Weeks + Cisplatin (Arm 1), IMRT 5 Weeks (Arm 2)
Comments End of RT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher Exact
Comments Two-sided significance level = 0.05
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection IMRT 6 Weeks + Cisplatin (Arm 1), IMRT 5 Weeks (Arm 2)
Comments One month after end of RT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.17
Comments [Not Specified]
Method Fisher Exact
Comments Two-sided significance level = 0.05
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection IMRT 6 Weeks + Cisplatin (Arm 1), IMRT 5 Weeks (Arm 2)
Comments Six months after end of RT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method Fisher Exact
Comments Two-side significance level = 0.05
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection IMRT 6 Weeks + Cisplatin (Arm 1), IMRT 5 Weeks (Arm 2)
Comments One year after end of RT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.26
Comments [Not Specified]
Method Fisher Exact
Comments Two-side significance level = 0.05
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection IMRT 6 Weeks + Cisplatin (Arm 1), IMRT 5 Weeks (Arm 2)
Comments Two years after the end of RT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.82
Comments [Not Specified]
Method Fisher Exact
Comments Two-side significance level = 0.05
6.Secondary Outcome
Title Mean One-year Total MD Anderson Dysphagia Inventory (MDADI) Score (Patient-reported Swallowing Outcome)
Hide Description The MDADI is a 20-item tool with each item scored as Strongly agree; Agree; No opinion; Disagree; or Strongly disagree. There is 1 global item (G1), 6 emotional subscale items (E2-E7), 5 functional subscale items (F1-F5), and 8 physical subscale items (P1-P8). For all items except E7 and F2, Strongly agree corresponds to a score of 1, Agree 2, No opinion 3, Disagree 4, and Strongly disagree 5. For E7 and F2, the scores are reversed; these 2 items are rescored to match the others before calculating summary scores. The composite (total) score is the mean of the 19 items (other than G1) X 20. Composite scores range from 20 to 100 with higher scores indicating less dysphagia.
Time Frame One year post-RT. Radiation therapy (RT) ends at approximately 6 weeks for Arm 1 and 5 weeks for Arm 2
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and eligible participants. Questionnaires were not completed by all participants. 121 Arm 1 and 106 Arm 2 participants had one year post-RT data.
Arm/Group Title IMRT 6 Weeks + Cisplatin (Arm 1) IMRT 5 Weeks (Arm 2)
Hide Arm/Group Description:

Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks

IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

IMRT 5 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy
Overall Number of Participants Analyzed 121 106
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
85.3
(82.5 to 88.1)
81.8
(79.0 to 84.5)
7.Secondary Outcome
Title Negative Predictive Value (NPV) of Post-treatment FDG-PET/CT Scan [Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT)] for Progression-free Survival and Local-regional Control at Two Years
Hide Description NPV is the percentage of participants alive and failure-free at 2 years among those with a negative post-treatment scan, as evaluated by central review. Negative scan determined as follows: primary site, right neck, left neck evaluated using a 5-point ordinal scale: 1-Definite complete metabolic response (CMR), 2-Likely CMR, 3-Likely inflammatory, 4-Likely residual metabolic disease (RMD), and 5-Definite RMD. 'Negative'= 1 or 2, 'Indeterminate'=3, 'Positive' = 4 or 5. 'Negative' for all three evaluation sites = overall score of 'Negative.' Progression (failure) is defined as local, regional, or distant disease progression (PR) or any death. Local-regional progression (failure) is defined as local or regional PR, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown > 20 weeks post RT, death due to study cancer or unknown causes without documented PR. The protocol specified that both arms would be combined for analysis.
Time Frame 3 months (scan) and two years after the end of RT (approximately 6 weeks for Arm 1 and 5 weeks for Arm 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and eligible participants with negative post-treatment PET
Arm/Group Title Both Arms Combined
Hide Arm/Group Description:

IMRT 6 Weeks + Cisplatin arm: Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks; Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy.

IMRT 5 weeks arm: Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy

Overall Number of Participants Analyzed 115
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
Progression-free Survival
92.0 [1] 
(87.7 to NA)
Local-regional failure
94.5 [2] 
(90.6 to NA)
[1]
One-sided interval
[2]
One-side interval
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Both Arms Combined
Comments Progression-free survival: The null hypothesis of negative predictive value ≤ 90% was tested against the alternative of > 90% with a 1-sided binomial test at the 0.10 level.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3
Comments [Not Specified]
Method binomial test
Comments One-sided significance level = 0.10
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Both Arms Combined
Comments Local-regional control: The null hypothesis of negative predictive value ≤ 90% was tested against the alternative of > 90% with a 1-sided binomial test at the 0.10 level.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments [Not Specified]
Method binomial test
Comments One-sided significance level = 0.10
8.Secondary Outcome
Title Human Papillomavirus (HPV) Deoxyribonucleic Acid (DNA) Detection Rate
Hide Description With a two-sided type error rate of 5% and based on chi-squared test for proportions, there is a greater than 99% power to detect HPV DNA detection rate of 65% and 95% between the 2 groups (n=140 in each arm). The rate of detection for each group will be summarized based on binomial distributions and a 95% confidence intervals (CI) will be provided.
Time Frame Baseline to up to 2 weeks after the completion of treatment
Outcome Measure Data Not Reported
9.Secondary Outcome
Title HPV DNA Rate Decline
Hide Description With a two-sided type error rate of 5% and based on paired t test for means, there is 99% power to detect HPV DNA rate decline of 0.375 (effect size) within each arm (n=140). The HPV DNA rate for each group will be summarized using means and standard deviations.
Time Frame Baseline to up to 2 weeks after the completion of treatment
Outcome Measure Data Not Reported
10.Secondary Outcome
Title HPV DNA Copy Number
Hide Description Correlation between HPV DNA copy number and the nodal metabolic volume will be calculated using Spearman's correlation coefficient and R2, and the corresponding 95% CI will be provided.
Time Frame Baseline to up to 2 weeks after the completion of treatment
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Variance for HPV DNA
Hide Description Univariable and multivariable cause specific analysis will be performed using the Cox proportional hazards model for rate of relapse.
Time Frame Baseline to up to 2 weeks after the completion of treatment
Outcome Measure Data Not Reported
Time Frame Weekly during treatment, at 1 and 3 months after end of treatment, then every 3 months from end of treatment for 2 years, every 6 months from end of treatment for 3 years, then annually until study completion. Maximum follow-up at time of reporting was 4.1 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title IMRT 6 Weeks + Cisplatin IMRT 5 Weeks
Hide Arm/Group Description

Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks

IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

IMRT 5 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy
All-Cause Mortality
IMRT 6 Weeks + Cisplatin IMRT 5 Weeks
Affected / at Risk (%) Affected / at Risk (%)
Total   6/152 (3.95%)   6/147 (4.08%) 
Hide Serious Adverse Events
IMRT 6 Weeks + Cisplatin IMRT 5 Weeks
Affected / at Risk (%) Affected / at Risk (%)
Total   31/152 (20.39%)   11/147 (7.48%) 
Blood and lymphatic system disorders     
Anemia  1  1/152 (0.66%)  0/147 (0.00%) 
Febrile neutropenia * 1  4/152 (2.63%)  0/147 (0.00%) 
Cardiac disorders     
Heart failure * 1  1/152 (0.66%)  0/147 (0.00%) 
Eye disorders     
Retinal detachment * 1  1/152 (0.66%)  0/147 (0.00%) 
Gastrointestinal disorders     
Constipation  1  1/152 (0.66%)  1/147 (0.68%) 
Dry mouth  1  1/152 (0.66%)  2/147 (1.36%) 
Dysphagia  1  4/152 (2.63%)  0/147 (0.00%) 
Esophagitis * 1  2/152 (1.32%)  0/147 (0.00%) 
Gastrointestinal pain * 1  0/152 (0.00%)  1/147 (0.68%) 
Oral pain * 1  1/152 (0.66%)  0/147 (0.00%) 
General disorders     
Fever * 1  2/152 (1.32%)  0/147 (0.00%) 
Flu like symptoms * 1  1/152 (0.66%)  0/147 (0.00%) 
Infusion related reaction * 1  1/152 (0.66%)  0/147 (0.00%) 
Pain  1  0/152 (0.00%)  2/147 (1.36%) 
Infections and infestations     
Appendicitis * 1  1/152 (0.66%)  0/147 (0.00%) 
Enterocolitis infectious * 1  0/152 (0.00%)  1/147 (0.68%) 
Lung infection * 1  1/152 (0.66%)  0/147 (0.00%) 
Mucosal infection * 1  2/152 (1.32%)  0/147 (0.00%) 
Sepsis * 1  1/152 (0.66%)  0/147 (0.00%) 
Investigations     
Creatinine increased * 1  1/152 (0.66%)  0/147 (0.00%) 
Lymphocyte count decreased  1  2/152 (1.32%)  0/147 (0.00%) 
Neutrophil count decreased * 1  1/152 (0.66%)  0/147 (0.00%) 
Metabolism and nutrition disorders     
Anorexia  1  4/152 (2.63%)  1/147 (0.68%) 
Dehydration * 1  2/152 (1.32%)  0/147 (0.00%) 
Hypocalcemia * 1  1/152 (0.66%)  0/147 (0.00%) 
Hypokalemia * 1  3/152 (1.97%)  0/147 (0.00%) 
Hypomagnesemia * 1  2/152 (1.32%)  0/147 (0.00%) 
Musculoskeletal and connective tissue disorders     
Neck soft tissue necrosis  1  1/152 (0.66%)  0/147 (0.00%) 
Nervous system disorders     
Dysarthria * 1  0/152 (0.00%)  1/147 (0.68%) 
Dysgeusia  1  0/152 (0.00%)  1/147 (0.68%) 
Headache * 1  0/152 (0.00%)  2/147 (1.36%) 
Presyncope * 1  1/152 (0.66%)  0/147 (0.00%) 
Syncope * 1  1/152 (0.66%)  1/147 (0.68%) 
Psychiatric disorders     
Confusion * 1  0/152 (0.00%)  1/147 (0.68%) 
Depression * 1  0/152 (0.00%)  1/147 (0.68%) 
Respiratory, thoracic and mediastinal disorders     
Aspiration * 1  3/152 (1.97%)  0/147 (0.00%) 
Pharyngeal mucositis  1  2/152 (1.32%)  0/147 (0.00%) 
Pharyngolaryngeal pain * 1  1/152 (0.66%)  0/147 (0.00%) 
Sore throat * 1  2/152 (1.32%)  0/147 (0.00%) 
Skin and subcutaneous tissue disorders     
Dry skin  1  0/152 (0.00%)  1/147 (0.68%) 
Rash maculo-papular * 1  1/152 (0.66%)  0/147 (0.00%) 
Vascular disorders     
Hypotension * 1  1/152 (0.66%)  0/147 (0.00%) 
Thromboembolic event * 1  6/152 (3.95%)  0/147 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
IMRT 6 Weeks + Cisplatin IMRT 5 Weeks
Affected / at Risk (%) Affected / at Risk (%)
Total   152/152 (100.00%)   147/147 (100.00%) 
Blood and lymphatic system disorders     
Anemia  1  92/152 (60.53%)  35/147 (23.81%) 
Ear and labyrinth disorders     
Ear pain * 1  8/152 (5.26%)  4/147 (2.72%) 
Hearing impaired  1  43/152 (28.29%)  34/147 (23.13%) 
Tinnitus  1  65/152 (42.76%)  41/147 (27.89%) 
Endocrine disorders     
Hypothyroidism * 1  18/152 (11.84%)  16/147 (10.88%) 
Gastrointestinal disorders     
Constipation  1  92/152 (60.53%)  53/147 (36.05%) 
Diarrhea  1  26/152 (17.11%)  14/147 (9.52%) 
Dry mouth  1  150/152 (98.68%)  142/147 (96.60%) 
Dyspepsia  1  42/152 (27.63%)  31/147 (21.09%) 
Dysphagia  1  124/152 (81.58%)  119/147 (80.95%) 
Gastroesophageal reflux disease * 1  8/152 (5.26%)  3/147 (2.04%) 
Gastrointestinal disorders - Other * 1  16/152 (10.53%)  13/147 (8.84%) 
Mucositis oral  1  131/152 (86.18%)  121/147 (82.31%) 
Nausea  1  109/152 (71.71%)  62/147 (42.18%) 
Oral pain * 1  9/152 (5.92%)  9/147 (6.12%) 
Vomiting  1  51/152 (33.55%)  30/147 (20.41%) 
General disorders     
Fatigue  1  138/152 (90.79%)  117/147 (79.59%) 
Fever * 1  9/152 (5.92%)  2/147 (1.36%) 
General disorders and administration site conditions - Other * 1  6/152 (3.95%)  11/147 (7.48%) 
Neck edema * 1  4/152 (2.63%)  10/147 (6.80%) 
Pain  1  115/152 (75.66%)  121/147 (82.31%) 
Infections and infestations     
Infections and infestations - Other * 1  12/152 (7.89%)  7/147 (4.76%) 
Mucosal infection * 1  10/152 (6.58%)  10/147 (6.80%) 
Injury, poisoning and procedural complications     
Dermatitis radiation  1  113/152 (74.34%)  109/147 (74.15%) 
Investigations     
Alanine aminotransferase increased * 1  14/152 (9.21%)  7/147 (4.76%) 
Aspartate aminotransferase increased * 1  12/152 (7.89%)  7/147 (4.76%) 
Blood bilirubin increased * 1  9/152 (5.92%)  5/147 (3.40%) 
Creatinine increased * 1  26/152 (17.11%)  3/147 (2.04%) 
Lymphocyte count decreased  1  118/152 (77.63%)  87/147 (59.18%) 
Neutrophil count decreased * 1  33/152 (21.71%)  3/147 (2.04%) 
Platelet count decreased * 1  53/152 (34.87%)  8/147 (5.44%) 
Weight loss  1  119/152 (78.29%)  101/147 (68.71%) 
White blood cell decreased * 1  56/152 (36.84%)  13/147 (8.84%) 
Metabolism and nutrition disorders     
Anorexia  1  81/152 (53.29%)  69/147 (46.94%) 
Dehydration * 1  23/152 (15.13%)  11/147 (7.48%) 
Hyperglycemia * 1  27/152 (17.76%)  13/147 (8.84%) 
Hyperkalemia * 1  9/152 (5.92%)  4/147 (2.72%) 
Hypoalbuminemia * 1  23/152 (15.13%)  11/147 (7.48%) 
Hypocalcemia * 1  14/152 (9.21%)  4/147 (2.72%) 
Hypokalemia * 1  16/152 (10.53%)  4/147 (2.72%) 
Hypomagnesemia * 1  31/152 (20.39%)  3/147 (2.04%) 
Hyponatremia * 1  33/152 (21.71%)  9/147 (6.12%) 
Musculoskeletal and connective tissue disorders     
Neck pain * 1  7/152 (4.61%)  11/147 (7.48%) 
Trismus  1  22/152 (14.47%)  25/147 (17.01%) 
Nervous system disorders     
Dizziness * 1  15/152 (9.87%)  8/147 (5.44%) 
Dysgeusia  1  142/152 (93.42%)  132/147 (89.80%) 
Headache * 1  12/152 (7.89%)  11/147 (7.48%) 
Peripheral sensory neuropathy  1  29/152 (19.08%)  15/147 (10.20%) 
Psychiatric disorders     
Anxiety * 1  11/152 (7.24%)  15/147 (10.20%) 
Depression * 1  12/152 (7.89%)  7/147 (4.76%) 
Insomnia  1  44/152 (28.95%)  34/147 (23.13%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  38/152 (25.00%)  37/147 (25.17%) 
Hiccups * 1  11/152 (7.24%)  0/147 (0.00%) 
Hoarseness * 1  18/152 (11.84%)  19/147 (12.93%) 
Pharyngeal mucositis  1  29/152 (19.08%)  44/147 (29.93%) 
Respiratory, thoracic and mediastinal disorders - Other * 1  8/152 (5.26%)  8/147 (5.44%) 
Sore throat * 1  42/152 (27.63%)  28/147 (19.05%) 
Voice alteration * 1  11/152 (7.24%)  13/147 (8.84%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  28/152 (18.42%)  25/147 (17.01%) 
Dry skin  1  36/152 (23.68%)  35/147 (23.81%) 
Skin and subcutaneous tissue disorders - Other * 1  12/152 (7.89%)  10/147 (6.80%) 
Skin hyperpigmentation * 1  3/152 (1.97%)  9/147 (6.12%) 
Vascular disorders     
Hypertension * 1  10/152 (6.58%)  11/147 (7.48%) 
Lymphedema * 1  11/152 (7.24%)  11/147 (7.48%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Wendy Seiferheld
Organization: NRG Oncology
Phone: 215-574-3208
EMail: seiferheldw@gmail.com
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Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT02254278    
Other Study ID Numbers: NRG-HN002
NCI-2014-01279 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-HN002 ( Other Identifier: NRG Oncology )
NRG-HN002 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Submitted: September 29, 2014
First Posted: October 1, 2014
Results First Submitted: June 25, 2020
Results First Posted: August 12, 2020
Last Update Posted: January 22, 2021