Clinical trial NCT00865098: Study of Cetuximab With Concomitant-boost Radiotherapy in Patients With Newly Diagnosed Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma of the Head and Neck
Keywords: Newly diagnosed locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2009-03-19
Enrollment: 27
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Completion Rate
timeFrame: time from first administration of cetuximab to last administration of cetuximab or RT (whichever is later), ≤ 9 weeks
Secondary outcomes:
measure: Best Response Rate
timeFrame: 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
measure: Safety - Number of Patients Experiencing Any Adverse Event
timeFrame: time from first dose up to 60 days after last dose of study treatment, ≤18 weeks
measure: Safety - Number of Patients Experiencing Any Grade 4 Adverse Event
timeFrame: time from first dose up to 60 days after last dose of study treatment, ≤18 weeks
measure: Safety - Number of Patients Experiencing Any Grade 3 or 4 Skin Reaction
timeFrame: time from first dose up to 60 days after last dose of study treatment, ≤18 weeks
measure: Safety - Number of Patients Experiencing Any Grade 3 or 4 Infusion Related Reaction
timeFrame: time from first dose up to 60 days after last dose of study treatment, ≤18 weeks
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Research Site
city: Chiba
country: Japan
facility: Research Site
city: Shizuoka
country: Japan
facility: Research Site
city: Tokyo
country: Japan
facility: Research Site
Study officials:
affiliation: Merck Serono Co.,Ltd, an Affilate of Merck Serono, Darmstadt, Germany
name: Masataka Ota, MD
role: STUDY_DIRECTOR
References:
citation: Okano S, Yoshino T, Fujii M, Onozawa Y, Kodaira T, Fujii H, Akimoto T, Ishikura S, Oguchi M, Zenda S, de Blas B, Tahara M, Beier F. Phase II study of cetuximab plus concomitant boost radiotherapy in Japanese patients with locally advanced squamous cell carcinoma of the head and neck. Jpn J Clin Oncol. 2013 May;43(5):476-82. doi: 10.1093/jjco/hyt030. Epub 2013 Mar 10.