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Phase III Trial to Assess Efficacy and Safety of Cetuximab for the Treatment of Chinese Participants With Head and Neck Cancer (CHANGE2)

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ClinicalTrials.gov Identifier: NCT02383966
Recruitment Status : Completed
First Posted : March 10, 2015
Results First Posted : April 16, 2019
Last Update Posted : May 13, 2022
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Squamous Cell of Head and Neck
Interventions Drug: Cetuximab
Drug: Cisplatin/Carboplatin
Drug: 5-fluorouracil
Enrollment 243
Recruitment Details First participant signed informed consent: 31 Jul 2015, Clinical data cut-off: 19 Jan 2018.
Pre-assignment Details  
Arm/Group Title Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil Cisplatin/Carboplatin + 5-Flurouracil
Hide Arm/Group Description Participants received Cetuximab as an intravenous infusion at an initial dose of 400 milligrams per square meter (mg/m^2) on Day 1 and a subsequent dose of 250 mg/m^2 on Day 8 and Day 15 of each 21-day treatment cycle. Cisplatin or Carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (5-FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles, post this participants without progressive disease (PD) continued to receive monotherapy with cetuximab until occurrence of disease progression or unacceptable toxicity. Participants received cisplatin or carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles.
Period Title: Overall Study
Started 164 79
Completed 138 72
Not Completed 26 7
Reason Not Completed
Ongoing at clinical cut-off date             25             4
Randomized, but not treated             1             3
Arm/Group Title Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil Cisplatin/Carboplatin + 5-Flurouracil Total
Hide Arm/Group Description Participants received Cetuximab as an intravenous infusion at an initial dose of 400 milligrams per square meter (mg/m^2) on Day 1 and a subsequent dose of 250 mg/m^2 on Day 8 and Day 15 of each 21-day treatment cycle. Cisplatin or Carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (5-FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles, post this participants without progressive disease (PD) continued to receive monotherapy with cetuximab until occurrence of disease progression or unacceptable toxicity. Participants received cisplatin or carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles. Total of all reporting groups
Overall Number of Baseline Participants 164 79 243
Hide Baseline Analysis Population Description
Intention-to-treat (ITT) analysis set included all participants who were randomized to study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 164 participants 79 participants 243 participants
57.1  (9.52) 57.0  (8.99) 57.1  (9.34)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 164 participants 79 participants 243 participants
Female
18
  11.0%
12
  15.2%
30
  12.3%
Male
146
  89.0%
67
  84.8%
213
  87.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 164 participants 79 participants 243 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
164
 100.0%
79
 100.0%
243
 100.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 164 participants 79 participants 243 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
164
 100.0%
79
 100.0%
243
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Progression-free Survival (PFS) Time, as Assessed by an Independent Review Committee (IRC)
Hide Description PFS time was defined as the time in months from the date of randomization until first observation of PD (based on imaging as assessed by IRC), or death due to any cause when death occurs within 60 days after the last tumor assessment or randomization (whichever is later). PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter. PFS was measured using Kaplan-Meier (KM) estimates.
Time Frame Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set included all participants who were randomized to study treatment.
Arm/Group Title Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil Cisplatin/Carboplatin + 5-Flurouracil
Hide Arm/Group Description:
Participants received Cetuximab as an intravenous infusion at an initial dose of 400 milligrams per square meter (mg/m^2) on Day 1 and a subsequent dose of 250 mg/m^2 on Day 8 and Day 15 of each 21-day treatment cycle. Cisplatin or Carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (5-FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles, post this participants without progressive disease (PD) continued to receive monotherapy with cetuximab until occurrence of disease progression or unacceptable toxicity.
Participants received cisplatin or carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles.
Overall Number of Participants Analyzed 164 79
Median (95% Confidence Interval)
Unit of Measure: months
5.5
(5.4 to 5.6)
4.2
(3.0 to 5.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil, Cisplatin/Carboplatin + 5-Flurouracil
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.566
Confidence Interval (2-Sided) 95%
0.400 to 0.803
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression-free Survival (PFS) Time, as Assessed by the Investigator
Hide Description PFS time was defined as the time in months from the date of randomization until first observation of PD (radiologically confirmed by Investigator), or death due to any cause when death occurs within 60 days after the last tumor assessment or randomization (whichever is later). PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter. PFS was measured using Kaplan-Meier (KM) estimates.
Time Frame Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set included all participants who were randomized to study treatment.
Arm/Group Title Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil Cisplatin/Carboplatin + 5-Flurouracil
Hide Arm/Group Description:
Participants received Cetuximab as an intravenous infusion at an initial dose of 400 milligrams per square meter (mg/m^2) on Day 1 and a subsequent dose of 250 mg/m^2 on Day 8 and Day 15 of each 21-day treatment cycle. Cisplatin or Carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (5-FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles, post this participants without progressive disease (PD) continued to receive monotherapy with cetuximab until occurrence of disease progression or unacceptable toxicity.
Participants received cisplatin or carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles.
Overall Number of Participants Analyzed 164 79
Median (95% Confidence Interval)
Unit of Measure: months
5.5
(5.5 to 5.7)
4.6
(2.9 to 5.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil, Cisplatin/Carboplatin + 5-Flurouracil
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.568
Confidence Interval (2-Sided) 95%
0.406 to 0.795
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Overall Survival (OS) Time
Hide Description The OS time was defined as the time from randomization to the date of death. If a participant was alive at the time of analysis, survival time was censored at the last date when the participant was known to be alive. If this date was after data cut-off, participants were censored at the date of data cut-off. OS was measured using Kaplan-Meier (KM) estimates.
Time Frame Time from date of randomization up to data cutoff (assessed up to 904 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set included all participants who were randomized to study treatment.
Arm/Group Title Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil Cisplatin/Carboplatin + 5-Flurouracil
Hide Arm/Group Description:
Participants received Cetuximab as an intravenous infusion at an initial dose of 400 milligrams per square meter (mg/m^2) on Day 1 and a subsequent dose of 250 mg/m^2 on Day 8 and Day 15 of each 21-day treatment cycle. Cisplatin or Carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (5-FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles, post this participants without progressive disease (PD) continued to receive monotherapy with cetuximab until occurrence of disease progression or unacceptable toxicity.
Participants received cisplatin or carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles.
Overall Number of Participants Analyzed 164 79
Median (95% Confidence Interval)
Unit of Measure: months
10.2
(9.3 to 11.5)
8.4
(6.5 to 9.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil, Cisplatin/Carboplatin + 5-Flurouracil
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.705
Confidence Interval (2-Sided) 95%
0.502 to 0.991
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Best Overall Response Rate (ORR)
Hide Description The Best ORR was based on imaging and classified according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. The BOR rate was defined as the number of participants whose BOR was either complete response (CR) or partial response (PR), relative to the number of participants belonging to the trial set of interest. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set included all participants who were randomized to study treatment.
Arm/Group Title Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil Cisplatin/Carboplatin + 5-Flurouracil
Hide Arm/Group Description:
Participants received Cetuximab as an intravenous infusion at an initial dose of 400 milligrams per square meter (mg/m^2) on Day 1 and a subsequent dose of 250 mg/m^2 on Day 8 and Day 15 of each 21-day treatment cycle. Cisplatin or Carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (5-FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles, post this participants without progressive disease (PD) continued to receive monotherapy with cetuximab until occurrence of disease progression or unacceptable toxicity.
Participants received cisplatin or carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles.
Overall Number of Participants Analyzed 164 79
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
50
(42.1 to 57.9)
26.6
(17.3 to 37.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil, Cisplatin/Carboplatin + 5-Flurouracil
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.76
Confidence Interval (2-Sided) 95%
1.52 to 5.45
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description The DCR was based on imaging and classified according to RECIST Version 1.1 criteria. The DCR was defined as the number of participants whose Best Overall Response is either CR, PR or stable disease (SD), divided by the number of participants belonging to the trial set of interest multiplied by 100. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on trial.
Time Frame Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set included all participants who were randomized to study treatment.
Arm/Group Title Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil Cisplatin/Carboplatin + 5-Flurouracil
Hide Arm/Group Description:
Participants received Cetuximab as an intravenous infusion at an initial dose of 400 milligrams per square meter (mg/m^2) on Day 1 and a subsequent dose of 250 mg/m^2 on Day 8 and Day 15 of each 21-day treatment cycle. Cisplatin or Carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (5-FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles, post this participants without progressive disease (PD) continued to receive monotherapy with cetuximab until occurrence of disease progression or unacceptable toxicity.
Participants received cisplatin or carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles.
Overall Number of Participants Analyzed 164 79
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
75.6
(68.3 to 82.0)
59.5
(47.9 to 70.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil, Cisplatin/Carboplatin + 5-Flurouracil
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.14
Confidence Interval (2-Sided) 95%
1.15 to 3.95
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR was determined for participants whose BOR was either CR or PR. It was defined as the time from the first assessment of CR or PR until the event defining PFS time. PFS time was defined as the time in months from the date of randomization until first observation of PD (based on imaging as assessed by IRC), or death due to any cause when death occurs within 60 days after the last tumor assessment or randomization (whichever is later). CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set included all participants who were randomized to study treatment.
Arm/Group Title Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil Cisplatin/Carboplatin + 5-Flurouracil
Hide Arm/Group Description:
Participants received Cetuximab as an intravenous infusion at an initial dose of 400 milligrams per square meter (mg/m^2) on Day 1 and a subsequent dose of 250 mg/m^2 on Day 8 and Day 15 of each 21-day treatment cycle. Cisplatin or Carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (5-FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles, post this participants without progressive disease (PD) continued to receive monotherapy with cetuximab until occurrence of disease progression or unacceptable toxicity.
Participants received cisplatin or carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles.
Overall Number of Participants Analyzed 164 79
Median (95% Confidence Interval)
Unit of Measure: Weeks
18.1
(13.1 to 20.3)
13.9
(8.7 to 18.1)
7.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Emergent Adverse Events Leading to Death and AEs Leading to Discontinuation
Hide Description An Adverse event (AE) was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs.
Time Frame Time from date of randomization up to data cutoff (assessed up to 904 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who had received at least 1 dose of any trial treatment.
Arm/Group Title Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil Cisplatin/Carboplatin + 5-Flurouracil
Hide Arm/Group Description:
Participants received Cetuximab as an intravenous infusion at an initial dose of 400 milligrams per square meter (mg/m^2) on Day 1 and a subsequent dose of 250 mg/m^2 on Day 8 and Day 15 of each 21-day treatment cycle. Cisplatin or Carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (5-FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles, post this participants without progressive disease (PD) continued to receive monotherapy with cetuximab until occurrence of disease progression or unacceptable toxicity.
Participants received cisplatin or carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles.
Overall Number of Participants Analyzed 163 76
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
163
 100.0%
75
  98.7%
TESAEs
46
  28.2%
21
  27.6%
TEAEs Leading to Death
11
   6.7%
8
  10.5%
AEs Leading to Discontinuation
27
  16.6%
8
  10.5%
Time Frame Time from date of randomization up to data cutoff (assessed up to 904 days)
Adverse Event Reporting Description Treatment emergent serious and non-serious adverse events are reported below.
 
Arm/Group Title Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil Cisplatin/Carboplatin + 5-Flurouracil
Hide Arm/Group Description Participants received Cetuximab as an intravenous infusion at an initial dose of 400 milligrams per square meter (mg/m^2) on Day 1 and a subsequent dose of 250 mg/m^2 on Day 8 and Day 15 of each 21-day treatment cycle. Cisplatin or Carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (5-FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles, post this participants without progressive disease (PD) continued to receive monotherapy with cetuximab until occurrence of disease progression or unacceptable toxicity. Participants received cisplatin or carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. After the administration of cisplatin or carboplatin, participants received 5-fluorouracil (FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. All treatments were administered up to a maximum of 6 treatment cycles.
All-Cause Mortality
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil Cisplatin/Carboplatin + 5-Flurouracil
Affected / at Risk (%) Affected / at Risk (%)
Total   105/163 (64.42%)   54/76 (71.05%) 
Hide Serious Adverse Events
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil Cisplatin/Carboplatin + 5-Flurouracil
Affected / at Risk (%) Affected / at Risk (%)
Total   46/163 (28.22%)   21/76 (27.63%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/163 (0.61%)  2/76 (2.63%) 
Febrile neutropenia * 1  0/163 (0.00%)  1/76 (1.32%) 
Thrombocytopenia * 1  2/163 (1.23%)  2/76 (2.63%) 
Cardiac disorders     
Atrial fibrillation * 1  0/163 (0.00%)  1/76 (1.32%) 
Cardiac arrest * 1  1/163 (0.61%)  0/76 (0.00%) 
Cardiac failure * 1  1/163 (0.61%)  0/76 (0.00%) 
Cardiopulmonary failure * 1  1/163 (0.61%)  0/76 (0.00%) 
Gastrointestinal disorders     
Diarrhoea * 1  2/163 (1.23%)  1/76 (1.32%) 
Dysphagia * 1  1/163 (0.61%)  0/76 (0.00%) 
Glossodynia * 1  1/163 (0.61%)  0/76 (0.00%) 
Haematemesis * 1  0/163 (0.00%)  1/76 (1.32%) 
Mouth ulceration * 1  1/163 (0.61%)  0/76 (0.00%) 
Oesophageal polyp * 1  1/163 (0.61%)  0/76 (0.00%) 
Stomatitis * 1  0/163 (0.00%)  1/76 (1.32%) 
Upper gastrointestinal haemorrhage * 1  1/163 (0.61%)  0/76 (0.00%) 
Vomiting * 1  1/163 (0.61%)  0/76 (0.00%) 
General disorders     
Death * 1  2/163 (1.23%)  0/76 (0.00%) 
Pain * 1  1/163 (0.61%)  0/76 (0.00%) 
Infections and infestations     
Infected fistula * 1  0/163 (0.00%)  1/76 (1.32%) 
Lung infection * 1  6/163 (3.68%)  4/76 (5.26%) 
Oral infection * 1  0/163 (0.00%)  1/76 (1.32%) 
Otitis media acute * 1  1/163 (0.61%)  0/76 (0.00%) 
Pneumonia * 1  2/163 (1.23%)  0/76 (0.00%) 
Septic shock * 1  0/163 (0.00%)  1/76 (1.32%) 
Soft tissue infection * 1  1/163 (0.61%)  0/76 (0.00%) 
Tracheostomy infection * 1  1/163 (0.61%)  0/76 (0.00%) 
Upper respiratory tract infection * 1  0/163 (0.00%)  2/76 (2.63%) 
Wound infection * 1  1/163 (0.61%)  0/76 (0.00%) 
Injury, poisoning and procedural complications     
Ankle fracture * 1  0/163 (0.00%)  1/76 (1.32%) 
Lower limb fracture * 1  1/163 (0.61%)  0/76 (0.00%) 
Vascular access complication * 1  1/163 (0.61%)  0/76 (0.00%) 
Investigations     
Acid base balance abnormal * 1  1/163 (0.61%)  0/76 (0.00%) 
Alanine aminotransferase increased * 1  1/163 (0.61%)  0/76 (0.00%) 
Aspartate aminotransferase increased * 1  1/163 (0.61%)  0/76 (0.00%) 
Blood creatinine increased * 1  1/163 (0.61%)  0/76 (0.00%) 
Gamma-glutamyltransferase increased * 1  1/163 (0.61%)  0/76 (0.00%) 
Neutrophil count decreased * 1  0/163 (0.00%)  1/76 (1.32%) 
Platelet count decreased * 1  1/163 (0.61%)  1/76 (1.32%) 
White blood cell count decreased * 1  0/163 (0.00%)  2/76 (2.63%) 
Metabolism and nutrition disorders     
Cachexia * 1  0/163 (0.00%)  1/76 (1.32%) 
Electrolyte imbalance * 1  1/163 (0.61%)  0/76 (0.00%) 
Hypokalaemia * 1  1/163 (0.61%)  0/76 (0.00%) 
Hypomagnesaemia * 1  2/163 (1.23%)  0/76 (0.00%) 
Musculoskeletal and connective tissue disorders     
Fistula * 1  0/163 (0.00%)  1/76 (1.32%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Oncologic complication * 1  0/163 (0.00%)  1/76 (1.32%) 
Tumor haemorrhage * 1  1/163 (0.61%)  3/76 (3.95%) 
Tumor pain * 1  1/163 (0.61%)  0/76 (0.00%) 
Nervous system disorders     
Cerebral infarction * 1  2/163 (1.23%)  0/76 (0.00%) 
Cerebrovascular insufficiency * 1  1/163 (0.61%)  0/76 (0.00%) 
Renal and urinary disorders     
Renal failure * 1  0/163 (0.00%)  1/76 (1.32%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure * 1  1/163 (0.61%)  0/76 (0.00%) 
Asthma * 1  1/163 (0.61%)  0/76 (0.00%) 
Dyspnoea * 1  5/163 (3.07%)  0/76 (0.00%) 
Haemoptysis * 1  1/163 (0.61%)  0/76 (0.00%) 
Laryngeal obstruction * 1  1/163 (0.61%)  0/76 (0.00%) 
Laryngeal oedema * 1  0/163 (0.00%)  1/76 (1.32%) 
Laryngeal pain * 1  1/163 (0.61%)  0/76 (0.00%) 
Obstructive airways disorder * 1  0/163 (0.00%)  2/76 (2.63%) 
Pleural effusion * 1  1/163 (0.61%)  0/76 (0.00%) 
Pneumonitis * 1  1/163 (0.61%)  0/76 (0.00%) 
Pulmonary embolism * 1  1/163 (0.61%)  0/76 (0.00%) 
Respiratory failure * 1  2/163 (1.23%)  0/76 (0.00%) 
Vascular disorders     
Deep vein thrombosis * 1  0/163 (0.00%)  1/76 (1.32%) 
Peripheral artery occlusion * 1  1/163 (0.61%)  0/76 (0.00%) 
Venous haemorrhage * 1  1/163 (0.61%)  0/76 (0.00%) 
Venous thrombosis limb * 1  1/163 (0.61%)  0/76 (0.00%) 
1
Term from vocabulary, MedDRA version 21.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil Cisplatin/Carboplatin + 5-Flurouracil
Affected / at Risk (%) Affected / at Risk (%)
Total   163/163 (100.00%)   73/76 (96.05%) 
Blood and lymphatic system disorders     
Anaemia * 1  73/163 (44.79%)  36/76 (47.37%) 
Leukopenia * 1  55/163 (33.74%)  24/76 (31.58%) 
Neutropenia * 1  58/163 (35.58%)  22/76 (28.95%) 
Thrombocytopenia * 1  23/163 (14.11%)  7/76 (9.21%) 
Cardiac disorders     
Palpitations * 1  7/163 (4.29%)  4/76 (5.26%) 
Gastrointestinal disorders     
Abdominal distension * 1  15/163 (9.20%)  3/76 (3.95%) 
Abdominal pain * 1  11/163 (6.75%)  1/76 (1.32%) 
Constipation * 1  73/163 (44.79%)  31/76 (40.79%) 
Diarrhoea * 1  44/163 (26.99%)  10/76 (13.16%) 
Gastrooesophageal reflux disease * 1  12/163 (7.36%)  1/76 (1.32%) 
Mouth ulceration * 1  30/163 (18.40%)  8/76 (10.53%) 
Nausea * 1  93/163 (57.06%)  51/76 (67.11%) 
Oral pain * 1  9/163 (5.52%)  3/76 (3.95%) 
Stomatitis * 1  44/163 (26.99%)  13/76 (17.11%) 
Vomiting * 1  60/163 (36.81%)  37/76 (48.68%) 
General disorders     
Asthenia * 1  40/163 (24.54%)  17/76 (22.37%) 
Chest discomfort * 1  10/163 (6.13%)  4/76 (5.26%) 
Facial pain * 1  2/163 (1.23%)  6/76 (7.89%) 
Fatigue * 1  9/163 (5.52%)  1/76 (1.32%) 
Pyrexia * 1  42/163 (25.77%)  12/76 (15.79%) 
Malaise * 1  12/163 (7.36%)  8/76 (10.53%) 
Infections and infestations     
Lung infection * 1  16/163 (9.82%)  2/76 (2.63%) 
Paronychia * 1  13/163 (7.98%)  0/76 (0.00%) 
Upper respiratory tract infection * 1  13/163 (7.98%)  4/76 (5.26%) 
Investigations     
Alanine aminotransferase increased * 1  12/163 (7.36%)  4/76 (5.26%) 
Aspartate aminotransferase increased * 1  9/163 (5.52%)  2/76 (2.63%) 
Blood creatinine increased * 1  4/163 (2.45%)  4/76 (5.26%) 
Haemoglobin decreased * 1  14/163 (8.59%)  5/76 (6.58%) 
Lymphocyte count decreased * 1  6/163 (3.68%)  5/76 (6.58%) 
Neutrophil count decreased * 1  47/163 (28.83%)  20/76 (26.32%) 
Platelet count decreased * 1  20/163 (12.27%)  11/76 (14.47%) 
Red blood cell count decreased * 1  11/163 (6.75%)  6/76 (7.89%) 
Weight decreased * 1  103/163 (63.19%)  31/76 (40.79%) 
Weight increased * 1  9/163 (5.52%)  3/76 (3.95%) 
White blood cell count decreased * 1  62/163 (38.04%)  25/76 (32.89%) 
White blood cell count increased * 1  4/163 (2.45%)  5/76 (6.58%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  67/163 (41.10%)  34/76 (44.74%) 
Hyperuricaemia * 1  1/163 (0.61%)  4/76 (5.26%) 
Hypoalbuminaemia * 1  22/163 (13.50%)  13/76 (17.11%) 
Hypocalcaemia * 1  32/163 (19.63%)  9/76 (11.84%) 
Hypochloraemia * 1  26/163 (15.95%)  12/76 (15.79%) 
Hypokalaemia * 1  56/163 (34.36%)  18/76 (23.68%) 
Hypomagnesaemia * 1  40/163 (24.54%)  7/76 (9.21%) 
Hyponatraemia * 1  44/163 (26.99%)  21/76 (27.63%) 
Hypoproteinaemia * 1  12/163 (7.36%)  6/76 (7.89%) 
Musculoskeletal and connective tissue disorders     
Neck pain * 1  12/163 (7.36%)  3/76 (3.95%) 
Nervous system disorders     
Dizziness * 1  23/163 (14.11%)  12/76 (15.79%) 
Headache * 1  10/163 (6.13%)  5/76 (6.58%) 
Poor quality sleep * 1  10/163 (6.13%)  5/76 (6.58%) 
Psychiatric disorders     
Depressed mood * 1  4/163 (2.45%)  7/76 (9.21%) 
Insomnia * 1  16/163 (9.82%)  4/76 (5.26%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  30/163 (18.40%)  12/76 (15.79%) 
Oropharyngeal pain * 1  15/163 (9.20%)  2/76 (2.63%) 
Productive cough * 1  21/163 (12.88%)  6/76 (7.89%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  9/163 (5.52%)  4/76 (5.26%) 
Dermatitis acneiform * 1  35/163 (21.47%)  0/76 (0.00%) 
Dry skin * 1  12/163 (7.36%)  0/76 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  12/163 (7.36%)  2/76 (2.63%) 
Pruritus * 1  15/163 (9.20%)  0/76 (0.00%) 
Rash * 1  77/163 (47.24%)  1/76 (1.32%) 
Vascular disorders     
Hypertension * 1  4/163 (2.45%)  5/76 (6.58%) 
Hypotension * 1  10/163 (6.13%)  1/76 (1.32%) 
1
Term from vocabulary, MedDRA version 21.0
*
Indicates events were collected by non-systematic assessment
[Not Specified]
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.
 
Results Point of Contact
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Name/Title: Communication Center
Organization: Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
EMail: service@emdgroup.com
Publications of Results:
Guo Y, Luo Y, Zhang Q, Huang X, Li Z, Shen L, Feng J, Sun Y, Yang K, Ge M, Zhu X, Wang L, Liu Y, He X, Bai C, Xue K, Zeng Y, Chang X, Chen W, Lin T. First-line treatment with chemotherapy plus cetuximab in Chinese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety results of the randomised, phase III CHANGE-2 trial. Eur J Cancer. 2021 Oct;156:35-45. doi: 10.1016/j.ejca.2021.06.039. Epub 2021 Aug 18.
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Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT02383966    
Other Study ID Numbers: EMR062202-060
First Submitted: March 4, 2015
First Posted: March 10, 2015
Results First Submitted: January 18, 2019
Results First Posted: April 16, 2019
Last Update Posted: May 13, 2022