A Trial to Determine the Safety and Anti-tumor Activity Profile of the Combination of Cetuximab and Concomitant Cisplatin Plus 5-Fluorouracil (5-FU) in Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma in Head and Neck (CHANGE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01177956
First received: June 2, 2010
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

The primary objective of this trial is to assess the antitumor activity and safety profile of cetuximab when given in combination with cisplatin + 5-Fluorouracil (5-FU) for the first-line treatment of recurrent and/or metastatic Squamous Cell Carcinoma in Head and Neck (SCCHN) in Asian subjects.


Condition Intervention Phase
Squamous Cell Carcinoma of the Head and Neck
Biological: Cetuximab
Drug: Cisplatin
Drug: 5-Fluorouracil
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label, Single-arm, Multicenter, Phase III Trial to Assess the Antitumor Activity and Safety Profile of Cetuximab When Given in Combination With Chemotherapy for the First-line Treatment of Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck in Asian Subjects

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Best Overall Response (BOR) Until Cut-off Date 25 January 2011 [ Time Frame: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 25 January 2011 ] [ Designated as safety issue: No ]
    BOR: Percentage of participants experiencing a Complete Response (CR) (complete disappearance of measurable and evaluable disease without new lesions) or Partial Response (PR) (greater than or equal to 50 percent decrease of sum of product diameters of measurable disease, evaluable disease not worsening or progressing, no new lesions confirmed by a subsequent assessment no less than 28 days after criteria for response were first met) (based on modified World Health Organization [WHO] criteria), divided by the number of participants belonging to intention to treat (ITT) or safety population.

  • Best Overall Response (BOR) Until Cut-off Date 15 November 2012 [ Time Frame: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012 ] [ Designated as safety issue: No ]
    BOR: Percentage of participants experiencing a CR (complete disappearance of measurable and evaluable disease without new lesions) or PR (greater than or equal to 50 percent decrease of sum of product diameters of measurable disease, evaluable disease not worsening or progressing, no new lesions confirmed by a subsequent assessment no less than 28 days after criteria for response were first met) (based on modified WHO criteria), divided by the number of participants belonging to ITT or safety population.


Secondary Outcome Measures:
  • Overall Survival (OS) Time Until Cut-off Date 15 November 2012 [ Time Frame: Time from randomization to death or last day known to be alive, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012 ] [ Designated as safety issue: No ]
    The OS time was defined as the time from first administration of trial treatment to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.

  • Progression-free Survival (PFS) Time Until Cut-off Date 25 January 2011 [ Time Frame: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 25 January 2011 ] [ Designated as safety issue: No ]
    Duration from first administration of trial treatment until progression (radiological or clinical, if radiological progression is not available) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Participants without event are censored on the date of last tumor assessment.

  • Progression-free Survival (PFS) Time Until Cut-off Date 15 November 2012 [ Time Frame: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012 ] [ Designated as safety issue: No ]
    Duration from first administration of trial treatment until progression (radiological or clinical, if radiological progression is not available) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Participants without event are censored on the date of last tumor assessment.

  • Time to Progression (TTP) Until Cut-off Date 25 January 2011 [ Time Frame: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 25 January 2011 ] [ Designated as safety issue: No ]
    Time from first administration of trial treatment to disease progression (radiological or clinical, if radiological progression is not available). Participants without event are censored on the date of last tumor assessment.

  • Time to Progression (TTP) Until Cut-off Date 15 November 2012 [ Time Frame: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012 ] [ Designated as safety issue: No ]
    Time from first administration of trial treatment to disease progression (radiological or clinical, if radiological progression is not available). Participants without event are censored on the date of last tumor assessment.

  • Duration of Response Until Cut-off Date 25 January 2011 [ Time Frame: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 25 January 2011 ] [ Designated as safety issue: No ]
    Time from first assessment of CR or PR to disease progression or death (within 60 days of last tumor assessment). Participants without event are censored on the date of last tumor assessment. Tumor assessments based on modified WHO criteria.

  • Duration of Response Until Cut-off Date 15 November 2012 [ Time Frame: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012 ] [ Designated as safety issue: No ]
    Time from first assessment of CR or PR to disease progression or death (within 60 days of last tumor assessment). Participants without event are censored on the date of last tumor assessment. Tumor assessments based on modified WHO criteria.


Enrollment: 73
Study Start Date: December 2009
Study Completion Date: November 2012
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab + Cisplatin + 5-Fluorouracil (5-FU) Biological: Cetuximab

The initial dose of cetuximab will be 400 milligram per square meter (mg/m^2) as an intravenous (IV) infusion over 120 minutes. Subsequent weekly doses will be 250 mg/m^2 as an IV infusion over 60 minutes.

Chemotherapy will be continued for up to a maximum of six 3-week cycles in the absence of progressive disease (PD) or unacceptable toxicity. All subjects will receive cetuximab treatment until the occurrence of PD or unacceptable toxicity to cetuximab.

Other Name: Erbitux®
Drug: Cisplatin
Subjects will receive 75 mg/m^2 cisplatin as an IV infusion over 60 minutes on day 1 of each 3-week treatment cycle.
Drug: 5-Fluorouracil
Subjects will receive 750 mg/m^2 per day 5-FU as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed written informed consent
  • Inpatient
  • Greater than or equal to (>=) 18 years of age
  • Histologically or cytologically confirmed diagnosis of SCCHN
  • Recurrent and/or metastatic SCCHN not suitable for local therapy
  • Presence of at least 1 measurable lesion identified either by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to modified WHO criteria
  • Karnofsky performance status (KPS) >= 80 percent at trial entry
  • Neutrophils >= 1.5*10^9 per liter (L), platelet count >= 100*10^9 per L, and hemoglobin >= 90 gram per liter (g/L)
  • Total bilirubin less than or equal to (<=) 2*upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=3*ULN
  • Serum creatinine <=133 micromole per liter (mcmol/L)
  • Serum calcium within normal range
  • Effective contraception if procreative potential exists (applicable for both male and female subjects)

Exclusion Criteria:

  • Prior systemic chemotherapy, except if given as part of a multimodal treatment which was completed more than 6 months prior to trial entry
  • Surgery (excluding prior diagnostic biopsy) or irradiation within 4 weeks before trial entry
  • Nasopharyngeal carcinoma
  • Active infection (infection requiring IV antibiotics), including active tuberculosis, or known and declared human immunodeficiency virus (HIV)
  • Uncontrolled diabetes mellitus, pulmonary fibrosis, acute pulmonary disorder, interstitial pneumonia, cardiac failure or liver failure
  • Uncontrolled hypertension defined as systolic blood pressure >=180 millimeter of mercury (mmHg) and/or diastolic blood pressure >=130 mmHg under resting conditions
  • Pregnancy (absence to be confirmed by serum beta human chorionic gonadotrophin [beta-HCG] test) or breastfeeding
  • Concomitant chronic systemic immune therapy or hormonal therapy as cancer therapy
  • Other concomitant anticancer therapies
  • Documented or symptomatic brain or leptomeningeal metastasis
  • Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency
  • Medical or psychological condition that would not permit the subject to complete the trial or sign informed consent
  • Known drug abuse (with the exception of alcohol abuse)
  • Known hypersensitivity or allergic reaction against any of the components of the trial treatment
  • Previous treatment with monoclonal antibody therapy, other signal transduction inhibitors or epidermal growth factor receptor (EGFR) targeting therapy
  • Previous or current other squamous cell carcinoma (SCC)
  • Evidence of previous other malignancy within the last 5 years
  • Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such
  • Intake of any investigational medication within 30 days before trial entry
  • Legal incapacity or limited legal capacity
  • Other significant disease that in the Investigator's opinion would exclude the subject from the trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01177956

Locations
China
Cancer Institute & Hospital, Chinese Academy of Medical Sciences
Beijing, China
Jilin Cancer Hospital
Changchun, China
The Xiangya 2nd Hospital of Central South University
Changsha City, China
Fuijan Provincial Tumor Hospital
Fuijian, China
Nanfang Hospital of Nanfang Medical University
Guangzhou, China
Sun Yat-Sen Univesity Cancer Center
Guangzhou, China
Zhejiang Provincial Tumor Hospital
Hangzhou, China
Jiangsu Cancer Hospital
Jiangsu, Nanjing, China
Tumor Hospital of Guangxi Zhuang Autonomous Region / The Tumor Affiliated Hospital of Guangxi Medical University
Nanning City, China
Fundan University Shanghai Cancer Center
Shanghai, China
Eye & ENT Hospital of Fundan University
Shanghai, China
Tongji Hospital of Tongji Medical College of Huazhong University of Science & Technology
Wuhan City, China
Xijing Hospital, the Fourth Military Medical University
Xi'an, China
Korea, Republic of
Clinical Trial Center of Medical Research Institute, Pusan National University Hospital
Busan, Korea, Republic of
Sponsors and Collaborators
Merck KGaA
  More Information

Publications:
Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01177956     History of Changes
Other Study ID Numbers: EMR62241_055
Study First Received: June 2, 2010
Results First Received: July 3, 2012
Last Updated: August 25, 2014
Health Authority: China: Ministry of Health
China: Food and Drug Administration

Keywords provided by Merck KGaA:
Recurrent and/or metastatic squamous cell carcinoma of the head and neck
1st-line
Cetuximab
Chemotherapy
EMR 62241 -055
Merck KGaA
Recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN)

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Carcinoma
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cetuximab
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014