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Study of Cetuximab With Concomitant-boost Radiotherapy in Patients With Newly Diagnosed Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)

This study has been completed.
Sponsor:
Information provided by:
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00865098
First received: March 18, 2009
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

This study is conducted in Japanese newly diagnosed locally advanced SCCHN patients in order to assess tolerability and feasibility of Cetuximab plus concomitant boost radiotherapy (RT) regimen (the study treatment) and its safety profile (i.e. AEs: adverse events). In addition, efficacy (i.e. anti-tumor effect) of the study treatment is also evaluated.


Condition Intervention Phase
Carcinoma of the Head and Neck
Drug: Cetuximab
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, Non-randomized, Non-controlled, Multicenter Phase II Study Investigating Cetuximab in Combination With Concomitant-boost Radiotherapy as First-line Treatment for Japanese Patients With Newly Diagnosed Locally Advanced SCCHN.

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Completion Rate [ Time Frame: time from first administration of cetuximab to last administration of cetuximab or RT (whichever is later), ≤ 9 weeks ] [ Designated as safety issue: Yes ]
    Number of subjects who complete ≥70% of Cetuximab planned dose administration in terms of relative dose intensity of Cetuximab and full dose of RT ≤2 weeks over planned schedule in terms of RT duration ≤8 weeks, divided by the the number of subjects in the ITT/Safety population


Secondary Outcome Measures:
  • Best Response Rate [ Time Frame: best response was determined at week 8 post radiotherapy, for subjects with complete or partial response a confirmation in week 12 post radiotherapy was required ] [ Designated as safety issue: No ]
    Number of subjects experiencing a Complete Response (complete disappearance of measurable and evaluable disease without new lesions) or Partial Response (>=50% decrease of the sum of the product diameters of measurable disease, evaluable disease not worsening or progressing, no new lesions) at 8 weeks post radiotherapy (confirmed by repeat assessment at week 12) based on imaging according to modified World Health Organisation criteria as assessed independently by the Efficacy and Safety Evaluation Committee, divided by the number of subjects in the ITT/safety population

  • Safety - Number of Patients Experiencing Any Adverse Event [ Time Frame: time from first dose up to 60 days after last dose of study treatment, ≤18 weeks ] [ Designated as safety issue: Yes ]
    Please refer to Adverse Events section for further details

  • Safety - Number of Patients Experiencing Any Grade 4 Adverse Event [ Time Frame: time from first dose up to 60 days after last dose of study treatment, ≤18 weeks ] [ Designated as safety issue: Yes ]
    Severity was assessed according to the toxicity criteria defined in the National Cancer Institute - Common Terminology Criteria for Adverse Event (NCI-CTCAE), Version 3.0, where grade 1 denoted mild, grade 2 moderate, grade 3 severe, and grade 4 lifethreatening or disabling. In the case of adverse events not contained within the NCI-CTCAE, the investigator was responsible for assessing the severity of the AE (grades 1 to 4) based on the jeopardy to the subject's health and well-being, and the ability of the subject to function during the event.

  • Safety - Number of Patients Experiencing Any Grade 3 or 4 Skin Reaction [ Time Frame: time from first dose up to 60 days after last dose of study treatment, ≤18 weeks ] [ Designated as safety issue: Yes ]
    Skin reactions were considered as adverse events of special interest and were evaluated in a special AE category composed of specific MedDRA preferred terms. Severity was assessed according to criteria defined in the NCI-CTCAE, Version 3.0, where grade 1 is mild, grade 2 moderate, grade 3 severe, and grade 4 lifethreatening or disabling.

  • Safety - Number of Patients Experiencing Any Grade 3 or 4 Infusion Related Reaction [ Time Frame: time from first dose up to 60 days after last dose of study treatment, ≤18 weeks ] [ Designated as safety issue: Yes ]
    Infusion related reactions were considered as adverse events of special interest and were evaluated in a special AE category composed of specific MedDRA preferred terms. Severity was assessed according to criteria defined in the NCI-CTCAE, Version 3.0, where grade 1 is mild, grade 2 moderate, grade 3 severe, and grade 4 lifethreatening or disabling.


Enrollment: 27
Study Start Date: March 2009
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab With Radiotherapy Drug: Cetuximab
Patients receive Cetuximab at an initial dose of 400 mg/m^2 of Cetuximab to be infused 6 or 7 days before starting radiotherapy, followed by subsequent weekly infusions at a dose of 250 mg/m^2 of Cetuximab and RT (72.0 Gy total in 42 fractions) for the next 6 weeks of the treatment course. Subjects will receive Cetuximab until radiographically documented progressive disease or unacceptable toxicity occurs or consent is withdrawn. If RT is delayed, administration of Cetuximab every 7 days is continued. If RT is discontinued for any reason, treatment with Cetuximab monotherapy every 7 days is continued.

  Eligibility

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

Inclusion Criteria:

  1. The patient has pathologically proven squamous cell carcinoma arising in the oropharynx, hypopharynx, or larynx.
  2. The patient has been confirmed Epidermal Growth Factor Receptor expressing in tumor specimen by immunohistochemistry.
  3. The patient has stage III or IV disease (Unio Internationalis Contra Cancrum / International Union against Cancer Tumor-Lymph Nodes-Metastases classification) with an expected survival of ≥ 12 months.
  4. The patient has at least bi-dimensionally measurable disease.
  5. The patient is medically suitable to withstand a course of the definitive radiation therapy.
  6. The patient aged ≥ 20 years old at informed consent
  7. The patient's Karnofsky performance status is ≥ 60
  8. Hemoglobin ≥ 9g/dL
  9. Neutrophil ≥ 1500/mm^3
  10. Platelet ≥ 100,000/mm^3
  11. Total Bilirubin ≤ 1.5 mg/dL
  12. Aspartate Aminotransferase ≤ 2 x the upper limit of normal
  13. Alanine Aminotransferase ≤ 2 x the upper limit of normal
  14. Serum creatinine ≤ 1.5 mg/dL
  15. Serum calcium concentration: within normality
  16. The patient is eligible if disease free from a previously treated malignancy for greater than three years.
  17. The patient agrees to use effective contraception if procreative potential exists.
  18. The patient has given signed informed consent
  19. The patient who is a Japanese with Japanese citizenship

Exclusion Criteria:

  1. The patient has evidence of distant metastatic disease. The patient who has any metastatic disease documented by Magnetic Resonance Imaging for the head and neck, and Computed Tomography for the chest and abdomen should be excluded.
  2. The patient has squamous cell carcinoma arising in the nasopharynx or oral cavity.
  3. The patient has received prior systemic chemotherapy within the last three years.
  4. The patient has undergone previous surgery for the tumor under study other than biopsy.
  5. The patient has received prior radiation therapy to the head and neck.
  6. The patient's radiation therapy is considered to be a part of a postoperative regimen following primary surgical resection.
  7. The patient is pregnant or breast feeding.
  8. The patient has received prior Cetuximab or murine monoclonal antibody (including chimeric antibody) therapy or a history of severe hypersensitivity to any component of Cetuximab solution for Injection.
  9. The patient has a medical or psychological condition that would not permit the patient to complete the study or sign informed consent (including drug abuse).
  10. The patient has uncontrolled diabetes mellitus, malignant hypertension, or liver failure.
  11. The patient has or has suffered from a pulmonary fibrosis, acute pulmonary disorder, or interstitial pneumonia.
  12. The patient has an active infection (infection requiring intravenous anti-bacterial, anti-fungus, or anti-viral agent), or known and declared Human Immunodeficiency Virus infection.
  13. The patient has a 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
  14. The patient has a dental disease which requires incision and drainage.
  15. The patient has active multiple cancers (excluding skin cancer except for melanoma, and carcinoma in situ of the cervix or the digestive tract) in the last 3 years.
  16. The patient has been received some investigational medication within 30 days before study entry.
  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: NCT00865098

Locations
Japan
Research Site
Aichi, Japan
Research Site
Chiba, Japan
Research Site
Shizuoka, Japan
Research Site
Tokyo, Japan
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Masataka Ota, MD Merck Serono Co.,Ltd, an Affilate of Merck Serono, Darmstadt, Germany
  More Information

Publications:
Responsible Party: Yoshiteru Kimura, Merck Serono Co., Ltd. Tokyo, Japan, an Affiliate of Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT00865098     History of Changes
Other Study ID Numbers: EMR 62241-053
Study First Received: March 18, 2009
Results First Received: June 23, 2011
Last Updated: February 10, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Merck KGaA:
Newly diagnosed locally advanced squamous cell carcinoma of the head and neck (SCCHN)

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Cetuximab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014