Study of Cetuximab in Combination With Chemotherapy in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00971932
First received: September 3, 2009
Last updated: March 10, 2014
Last verified: March 2014
  Purpose

The primary objective of this trial is to assess the antitumor activity 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 of the head and neck (SCCHN) in Japanese subjects.


Condition Intervention Phase
Squamous Cell Carcinoma of the Head and Neck
Drug: Cetuximab
Drug: Cisplatin/Carboplatin
Drug: 5-Fluorouracil
Phase 2

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 II Study Investigating Cetuximab in Combination With Chemotherapy in the First-line Treatment of Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) in Japanese Subjects

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Best Overall Response (BOR) According to Modified World Health Organization (WHO) Criteria [ Time Frame: Evaluations performed every 6 weeks until progressive disease (PD) reported between day of first participant treated, until cut-off date, 02 March 2011 ] [ Designated as safety issue: No ]
    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 in the sum of the products of diameters [SOPD] of index lesions compared to the baseline SOPD, with no evidence of PD) confirmed by a subsequent assessment no less than 28 days after criteria for response were first met based on modified WHO criteria as assessed by Independent Review Committee (IRC).


Secondary Outcome Measures:
  • Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria [ Time Frame: Evaluations performed every 6 weeks until PD reported between day of first participant treated, until cut-off date, 02 March 2011 ] [ Designated as safety issue: No ]
    Percentage of participants with objective response based assessment of confirmed CR or confirmed PR according to RECIST as assessed by IRC. CR are those that persist on repeat imaging study at least 28 days after initial documentation of response. PR are those with greater than or equal to 30 percent decrease in the SOPD of index lesions compared to the baseline SOPD, with no evidence of PD.

  • Disease Control Rate [ Time Frame: Evaluations performed every 6 weeks until PD reported between day of first participant treated, until cut-off date, 02 March 2011 ] [ Designated as safety issue: No ]
    Percentage of participants experiencing a CR (complete disappearance of measurable and evaluable disease without new lesions) or PR (>=50 percent decrease in sum of the products of diameters [SOPD] of index lesions compared to baseline SOPD, with no evidence of PD) confirmed by subsequent assessment no less than 28 days after criteria for response were first met) or stable disease [SD] (neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD) at least once no less than 42 days after first dose of trial treatment based on modified WHO criteria as assessed by IRC.

  • Duration of Response [ Time Frame: Time from first assessment of CR or PR to PD, death or last tumor assessment, reported between day of first participant treated, until cut-off date, 02 March 2011 ] [ Designated as safety issue: No ]
    Duration of response according to modified WHO criteria as assessed by IRC was defined as the time from the first assessment of CR or PR until the date of the first occurrence of PD, or until the date of death when death occurred within 60 days of the last tumor assessment or first administration of trial treatment (whichever was last).

  • Progression-Free Survival (PFS) Time [ Time Frame: Time from first administration of trial treatment to PD, death or last tumor assessment, reported between day of first participant treated, until cut-off date, 02 March 2011 ] [ Designated as safety issue: No ]
    The PFS time according to modified WHO criteria as assessed by IRC was defined as duration from first administration of trial treatment until PD (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.

  • Overall Survival (OS) Time [ Time Frame: Time from first administration of trial treatment or last day known to be alive, reported between day of first participant treated, until cut-off date, 02 March 2011 ] [ Designated as safety issue: No ]
    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.

  • Time to Treatment Failure [ Time Frame: Time from first administration of trial treatment to treatment failure or last tumor assessment, reported between day of first participant treated, until cut-off date, 02 March 2011 ] [ Designated as safety issue: No ]
    Time to treatment failure according to modified WHO criteria as assessed by IRC was defined as the time from first administration of trial treatment until the date of the first occurrence of one of the events defining treatment failure: PD assessed by the investigator, discontinuation of treatment due to PD, discontinuation of treatment due to an adverse event (AE), start of any new anticancer therapy, or withdrawal of consent or death within 60 days of the last tumor assessment or first administration of trial treatment.


Enrollment: 33
Study Start Date: July 2009
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab + Cisplatin/Carboplatin + Fluorouracil (5-FU) Drug: 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.
Drug: Cisplatin/Carboplatin
Subjects will receive 100 mg/m^2 cisplatin as an IV infusion over 60 minutes on day 1 of each 3-week treatment cycle. If subject developed non-hematological toxicities to cisplatin, carboplatin (area under curve 5 [AUC5]) will be administered as an IV infusion over 60 to 120 minutes on Day 1 of each 3-week treatment cycle.
Drug: 5-Fluorouracil
Subjects will receive 1000 mg/m^2 per day 5-FU as a continuous IV infusion over 24 hours from day 1 to day 4 of each 3-week treatment cycle.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed diagnosis of SCCHN
  2. Confirmed epidermal growth factor receptor (EGFR) expression in tumor tissue by immunohistochemistry (IHC)
  3. Expected survival is more than 6 months
  4. Presence of at least 1 bidimensionally measurable lesion either by computed tomography (CT) scan or magnetic resonance imaging (MRI)
  5. Recurrent and/or metastatic SCCHN not suitable for local therapy
  6. Greater than or equal to (>=) 20 years of age
  7. Karnofsky performance status (KPS) >= 70% at trial entry
  8. Neutrophils: >= 1500 per millimeter^3 (1,500/mm^3); platelet count >= 100,000/mm^3; and hemoglobin >= 9 gram per deciliter (g/dL)
  9. Total bilirubin less than or equal to (<=) 2 * upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3 * ULN
  10. Creatinine clearance >60 milliliter per minute (mL/min).Calculated based on formulae such as the Cockroft-Gault formula for creatinine clearance
  11. Serum calcium within normal range (If serum albumin < 4.0 g/dL, the following adjusted serum calcium concentration should be within normality: Adjusted serum calcium concentration = actual serum calcium (milligram per deciliter [mg/dL]) - 0.8 * [actual serum albumin (g/dL) - 4]
  12. Effective contraception if risk of conception exists (applicable for both male and female subjects)
  13. Signed written informed consent
  14. Japanese (with Japanese citizenship)

Exclusion Criteria:

  1. Nasopharyngeal carcinoma
  2. Prior systemic chemotherapy, except if given as part of a multimodal treatment, which was completed more than 6 months prior to trial entry
  3. Surgery (excluding prior diagnostic biopsy) or irradiation within 4 weeks before trial entry
  4. Pregnancy (absence to be confirmed by serum/urine human chorionic gonadotropin [HCG] test) or breastfeeding
  5. Known hypersensitivity or allergic reaction against any of the components of the trial treatment including excipients
  6. Uncontrolled diabetes, malignant hypertension (defined as systolic blood pressure >= 180 millimeter of mercury [mmHg] and/or diastolic blood pressure >= 130 mmHg under resting conditions) or liver failure
  7. Pulmonary fibrosis, acute lung injury or interstitial pneumonia, or with previous medical history of these states
  8. Active infection, (infection requiring IV antibiotics, antibacterial, antifungal, or antiviral agent), including active tuberculosis, or known and declared human immunodeficiency virus (HIV)
  9. 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
  10. Current other squamous cell carcinoma (SCC) or previous other malignancy (excluding skin cancer except for melanoma and carcinoma in situ of the cervix or digestive tract) within the last 5 years
  11. Intake of any investigational medication within 30 days before trial entry
  12. Other concomitant anticancer therapies
  13. Documented or symptomatic brain or leptomeningeal metastasis
  14. Medical or psychological condition that would not permit the subject to complete the trial or sign informed consent including known drug abuse
  15. Previous treatment with monoclonal antibody therapy, other signal transduction inhibitors or EGFR targeting therapy
  16. Legal incapacity or limited legal capacity
  17. Other protocol-defined exclusion criteria may apply
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00971932

Locations
Japan
Research Site
Aichi, Japan
National Cancer Center East Hospital
Chiba, Japan
Research Site
Ehime, Japan
Research Site
Hokkaido, Japan
Tokai University
Kanagawa, Japan
Research Site
Kanagawa, Japan
Research Site
Osaka, Japan
Research Site
Shizuoka, Japan
Research Site
Tochigi, Japan
Research Site
Tokyo, Japan
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Mark P. Smith, MD Merck Serono Co., Ltd., Japan
  More Information

Publications:
Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00971932     History of Changes
Other Study ID Numbers: EMR 62241-056
Study First Received: September 3, 2009
Results First Received: July 4, 2012
Last Updated: March 10, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Merck KGaA:
Recurrent and/or metastatic
SCCHN

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

ClinicalTrials.gov processed this record on April 16, 2014