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)

• ClinicalTrials.gov Identifier: NCT01177956
• Recruitment Status: Completed
• First Posted: August 9, 2010
• Results First Posted: August 10, 2012
• Last Update Posted: September 3, 2014
• Sponsor: Merck KGaA, Darmstadt, Germany
• Information provided by (Responsible Party): Merck KGaA, Darmstadt, Germany

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Squamous Cell Carcinoma of the Head and Neck	Biological: Cetuximab; Drug: Cisplatin; Drug: 5-Fluorouracil	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 73 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: December 2009
• Actual Primary Completion Date: January 2011
• Actual Study Completion Date: November 2012

Arms and Interventions

Arm

Intervention/treatment

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.

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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.
2. 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 ]
   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 :

1. 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 ]
   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.
2. 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 ]
   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.
3. 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 ]
   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.
4. 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 ]
   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.
5. 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 ]
   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.
6. 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 ]
   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.
7. 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 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Eye & ENT Hospital of Fundan University

Shanghai, China

Fundan University Shanghai Cancer Center

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, Darmstadt, Germany

More Information

Publications of Results:

Guo Y, Shi M, Yang A, Feng J, Zhu X, Choi YJ, Hu G, Pan J, Hu C, Luo R, Zhang Y, Zhou L, Cheng Y, Lüpfert C, Cai J, Shi Y. Platinum-based chemotherapy plus cetuximab first-line for Asian patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Results of an open-label, single-arm, multicenter trial. Head Neck. 2015 Aug;37(8):1081-7. doi: 10.1002/hed.23707. Epub 2014 Sep 17.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT01177956
• Other Study ID Numbers: EMR62241_055
• First Posted: August 9, 2010
• Results First Posted: August 10, 2012
• Last Update Posted: September 3, 2014
• Last Verified: August 2014

Keywords provided by Merck KGaA, Darmstadt, Germany:

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; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Neoplasms by Site; Fluorouracil; Cetuximab; Antineoplastic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Immunological