Back to resultsPhase III Trial to Assess Efficacy and Safety of Cetuximab for the Treatment of Chinese Participants With Head and Neck Cancer (CHANGE2)
Primary Purpose
Carcinoma, Squamous Cell of Head and Neck
Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Cetuximab
Cisplatin/Carboplatin
5-fluorouracil
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Squamous Cell of Head and Neck
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of SCCHN
- Recurrent and/or metastatic SCCHN, not suitable for local-regional treatment
- Presence of at least 1 measurable lesion according to RECIST Version 1.1
- Signed written informed consent before any trial-related activities are carried out
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Other protocol-defined inclusion criteria could apply
Exclusion Criteria:
- Prior systemic chemotherapy, except if given as part of multimodal treatment for locally advanced disease, that was completed within 6 months before randomization
- Surgery (excluding prior biopsy for diagnosis) or irradiation within 4 weeks before trial entry
- Previous treatment with monoclonal antibody or signal transduction inhibitors targeting epidermal growth factor receptor
- Nasopharyngeal carcinoma
- Known central nervous system metastasis and/or leptomeningeal disease
- Medical or psychological condition that would not permit the participant to complete the trial or sign informed consent
- Legal incapacity or limited legal capacity
- Other protocol-defined exclusion criteria could apply
Sites / Locations
- Research site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil
Cisplatin/Carboplatin + 5-Flurouracil
Arm Description
Outcomes
Primary Outcome Measures
Progression-free Survival (PFS) Time, as Assessed by an Independent Review Committee (IRC)
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.
Secondary Outcome Measures
Progression-free Survival (PFS) Time, as Assessed by the Investigator
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.
Overall Survival (OS) Time
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.
Best Overall Response Rate (ORR)
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.
Disease Control Rate (DCR)
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.
Duration of Response (DOR)
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.
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
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.
Full Information
NCT ID
NCT02383966
First Posted
March 4, 2015
Last Updated
April 19, 2022
Sponsor
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT02383966
Brief Title
Phase III Trial to Assess Efficacy and Safety of Cetuximab for the Treatment of Chinese Participants With Head and Neck Cancer
Acronym
CHANGE2
Official Title
A Multicenter, Randomized, Open-label, Phase III Trial to Assess Efficacy and Safety of Cetuximab When Given in Combination With Cisplatin Plus 5 Fluorouracil Versus Cisplatin Plus 5-fluorouracil Alone for the First-line Treatment of Chinese Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
July 31, 2015 (Actual)
Primary Completion Date
January 19, 2018 (Actual)
Study Completion Date
December 20, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This trial aimed to assess efficacy and safety of cetuximab when given in combination with chemotherapy compared with chemotherapy alone in Chinese participants with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) as the first-line treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Squamous Cell of Head and Neck
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
243 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil
Arm Type
Experimental
Arm Title
Cisplatin/Carboplatin + 5-Flurouracil
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
Cisplatin/Carboplatin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
5-fluorouracil
Other Intervention Name(s)
5-FU
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS) Time, as Assessed by an Independent Review Committee (IRC)
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)
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS) Time, as Assessed by the Investigator
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)
Title
Overall Survival (OS) Time
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)
Title
Best Overall Response Rate (ORR)
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)
Title
Disease Control Rate (DCR)
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)
Title
Duration of Response (DOR)
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)
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
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed diagnosis of SCCHN
Recurrent and/or metastatic SCCHN, not suitable for local-regional treatment
Presence of at least 1 measurable lesion according to RECIST Version 1.1
Signed written informed consent before any trial-related activities are carried out
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Other protocol-defined inclusion criteria could apply
Exclusion Criteria:
Prior systemic chemotherapy, except if given as part of multimodal treatment for locally advanced disease, that was completed within 6 months before randomization
Surgery (excluding prior biopsy for diagnosis) or irradiation within 4 weeks before trial entry
Previous treatment with monoclonal antibody or signal transduction inhibitors targeting epidermal growth factor receptor
Nasopharyngeal carcinoma
Known central nervous system metastasis and/or leptomeningeal disease
Medical or psychological condition that would not permit the participant to complete the trial or sign informed consent
Legal incapacity or limited legal capacity
Other protocol-defined exclusion criteria could apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Research site
City
Darmstadt
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
34418665
Citation
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.
Results Reference
result
Links:
URL
https://clinicaltrials.emdgroup.com/en/trial-details/?id=EMR062202-060
Description
Trial Awareness and Transparency website
Learn more about this trial
Phase III Trial to Assess Efficacy and Safety of Cetuximab for the Treatment of Chinese Participants With Head and Neck Cancer
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