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

April 19, 2022 updated by: Merck KGaA, Darmstadt, Germany

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

243

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Darmstadt, Germany
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil
Drug: Cetuximab
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.
Other Names:
  • Erbitux
Drug: Cisplatin/Carboplatin
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.
Drug: 5-fluorouracil
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.
Other Names:
  • 5-FU
Active Comparator: Cisplatin/Carboplatin + 5-Flurouracil
Drug: Cisplatin/Carboplatin
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.
Drug: 5-fluorouracil
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.
Other Names:
  • 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
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)
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 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)
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.
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)
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.
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)
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.
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)
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 from date of randomization up to data cutoff (assessed up to 904 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck KGaA, Darmstadt, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 31, 2015

Primary Completion (Actual)

January 19, 2018

Study Completion (Actual)

December 20, 2021

Study Registration Dates

First Submitted

March 4, 2015

First Submitted That Met QC Criteria

March 4, 2015

First Posted (Estimate)

March 10, 2015

Study Record Updates

Last Update Posted (Actual)

May 13, 2022

Last Update Submitted That Met QC Criteria

April 19, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EMR062202-060

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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