Carcinoma, Squamous Cell of Head and NeckPhase 3CHANGE2NCT02383966
Phase III Trial to Assess Efficacy and Safety of Cetuximab for the Treatment of Chinese Participants With Head and Neck Cancer
A Phase 3 study testing Cetuximab, Cisplatin/Carboplatin and 5-fluorouracil in people with Carcinoma, Squamous Cell of Head and Neck, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Squamous Cell of Head and Neck
- What is being tested?
- Cetuximab, Cisplatin/Carboplatin and 5-fluorouracil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 243 participants
- Where
- 1 siteGermany
- Study dates
- 31 Jul 2015to 20 Dec 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Being tested
- Cetuximab, Cisplatin/Carboplatin, 5-fluorouracil
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
Also called Erbitux
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/CarboplatinDrug
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.
5-fluorouracilDrug
Also called 5-FU
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.
| Study group | Role | What they receive |
|---|---|---|
| Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil | Experimental | Not described Receives: Drug: Cetuximab; Drug: Cisplatin/Carboplatin; Drug: 5-fluorouracil |
| Cisplatin/Carboplatin + 5-Flurouracil | Active comparator | Not described Receives: Drug: Cisplatin/Carboplatin; Drug: 5-fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
Secondary outcomes (6)
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.
Measured: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
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.
Measured: Time from date of randomization up to data cutoff (assessed up to 904 days)
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.
Measured: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
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.
Measured: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
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.
Measured: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
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.
Measured: Time from date of randomization up to data cutoff (assessed up to 904 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2015 (estimated)
- Study start31 Jul 2015
- Primary completion19 Jan 2018
- Study completion20 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Squamous Cell of Head and NeckStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 243 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02383966
- Sponsor's protocol ID
- EMR062202-060
- Acronym
- CHANGE2
- Status last verified
- Apr 2022
- First submitted
- 4 Mar 2015
- Last updated
- 13 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 34418665
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02383966
- Acronym / sponsor ID
- CHANGE2 / EMR062202-060
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 243 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 31 Jul 2015 (actual)
- Primary completion
- 19 Jan 2018 (actual)
- Study completion
- 20 Dec 2021 (actual)
- First posted
- 10 Mar 2015 (estimated)
- Results
- Posted 16 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil | Experimental | Drug: Cetuximab, Drug: Cisplatin/Carboplatin, Drug: 5-fluorouracil |
| Cisplatin/Carboplatin + 5-Flurouracil | Active comparator | Drug: Cisplatin/Carboplatin, Drug: 5-fluorouracil |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CetuximabAlso: ErbituxParticipants 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. | Drug | Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil |
| Cisplatin/CarboplatinCisplatin 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. | Drug | Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil, Cisplatin/Carboplatin + 5-Flurouracil |
| 5-fluorouracilAlso: 5-FUParticipants 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. | Drug | Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil, Cisplatin/Carboplatin + 5-Flurouracil |
Primary outcome
Progression-free Survival (PFS) Time, as Assessed by an Independent Review Committee (IRC)
Time frame: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
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.
6 secondary outcomes
Progression-free Survival (PFS) Time, as Assessed by the Investigator
Time frame: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
Overall Survival (OS) Time
Time frame: Time from date of randomization up to data cutoff (assessed up to 904 days)
Best Overall Response Rate (ORR)
Time frame: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
Disease Control Rate (DCR)
Time frame: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
Duration of Response (DOR)
Time frame: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)
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
Time frame: Time from date of randomization up to data cutoff (assessed up to 904 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34418665Guo 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.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- Medical Information Location Map - Med Info ContactsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck KGaA, Darmstadt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cetuximab, Cisplatin/Carboplatin and 5-fluorouracil in people with Carcinoma, Squamous Cell of Head and Neck, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) Time, as Assessed by an Independent Review Committee (IRC) (time frame: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02383966, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2022.