A Study in Head and Neck Cancer

• Overall survival (OS) [ Time Frame: Randomization to date of death from any cause ] [ Designated as safety issue: No ]
• Progression-free survival (PFS) [ Time Frame: Randomization to the first date of objective progression of disease or death from any cause ] [ Designated as safety issue: No ]
• Proportion of patients having a confirmed best response of Partial Response (PR) or Complete Response (CR) [ Time Frame: Randomization to progression of disease ] [ Designated as safety issue: No ]
• Plasma concentration of Cetuximab [ Time Frame: Cycle 1, week 1: 0 (immediately after), 1, 2 and 24 h (post-doses). Any 4 doses between Cycle 1, week 3 and Cycle 3 week 3: 0 (immediately after), 24, 96 and 168 h (post-doses) ] [ Designated as safety issue: No ]
• Anti-Cetuximab Antibodies [ Time Frame: Day 1 of Week 1 in Cycles 1, 3, and 5, and at the 30-day follow-up visit after the end of treatment ] [ Designated as safety issue: No ]
• Proportion of patients having a confirmed best response of PR or CR, or best response of stable disease (SD) [ Time Frame: Randomization to progression of disease ] [ Designated as safety issue: No ]
• Cmax of Cetuximab [ Time Frame: Cycle 1, week 1: 0 (immediately after), 1, 2 and 24 h (post-doses). Any 4 doses between Cycle 1, week 3 and Cycle 3 week 3: 0 (immediately after), 24, 96 and 168 h (post-doses) ] [ Designated as safety issue: No ]
• AUC of Cetuximab [ Time Frame: Cycle 1, week 1: 0 (immediately after), 1, 2 and 24 h (post-doses). Any 4 doses between Cycle 1, week 3 and Cycle 3 week 3: 0 (immediately after), 24, 96 and 168 h (post-doses) ] [ Designated as safety issue: No ]

This study will begin with a 30 patients lead-in part: these 30 patients will receive Cetuximab manufactured by ImClone on a weekly basis in combination with other chemotherapy drugs (Cisplatin or Carboplatin plus 5-Fluorouracil) administered every 3 weeks. After 18 weeks, patients who benefit from this treatment may continue to receive cetuximab once-weekly until progression of the disease, an unacceptable side effect occurs, patients withdraw consent, or the study is closed.

In the second part of this study, 200 patients will be randomize in 2 arms:

• 100 patients will receive commercial cetuximab manufactured by ImClone (Group A)
• 100 patients will receive cetuximab manufactured by Boehringer Ingelheim (Group B.

All these 200 patients will receive other chemotherapy drugs (Cisplatin or Carboplatin plus 5-Fluorouracil) administered every 3 weeks. After 18 weeks, patients who benefit from this treatment may continue to receive cetuximab once-weekly until progression of the disease, an unacceptable side effect occurs, patients withdraw consent, or the study is closed.

• Drug: cetuximab
  Administered intravenously
  Other Names:

  • Erbitux
  • LY2939777
• Drug: Cisplatin
  Administered intravenously
• Drug: Carboplatin
  Administered intravenously
• Drug: 5-fluorouracil
  Administered intravenously

• Experimental: Cetuximab manufactured by Boehringer Ingelheim

  Cycle 1:

  Week 1 - Cetuximab 400 mg/m2 on day 1; Cisplatin 100 mg/m2 on day 1 or Carboplatin AUC 5 on day 1; 5-FU 1000 mg/m2 on days 1-4

  Week 2 - Cetuximab 250 mg/m2 on day 1

  Week 3 - Cetuximab 250 mg/m2 on day 1

  Cycle 2 - 6:

  Week 1 - Cetuximab 250 mg/m2 on day 1; Cisplatin 100 mg/m2 on day 1 or Carboplatin AUC 5 on day 1; 5-FU 1000 mg/m2 on days 1-4

  Week 2 - Cetuximab 250 mg/m2 on day 1

  Week 3 - Cetuximab 250 mg/m2 on day 1

  After 6 cycles, patients may then receive weekly Cetuximab monotherapy 250 mg/m2 until progression of disease, unacceptable toxicity, or another withdrawal criteria is met.

  Interventions:

  • Drug: cetuximab
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: 5-fluorouracil
• Experimental: Cetuximab manufactured by ImClone

  Cycle 1:

  Week 1 - Cetuximab 400 mg/m2 on day 1; Cisplatin 100 mg/m2 on day 1 or Carboplatin AUC 5 on day 1; 5-FU 1000 mg/m2 on days 1-4

  Week 2 - Cetuximab 250 mg/m2 on day 1

  Week 3 - Cetuximab 250 mg/m2 on day 1

  Cycle 2 - 6:

  Week 1 - Cetuximab 250 mg/m2 on day 1; Cisplatin 100 mg/m2 on day 1 or Carboplatin AUC 5 on day 1; 5-FU 1000 mg/m2 on days 1-4

  Week 2 - Cetuximab 250 mg/m2 on day 1

  Week 3 - Cetuximab 250 mg/m2 on day 1

  After 6 cycles, patients may then receive weekly Cetuximab monotherapy 250 mg/m2 until progression of disease, unacceptable toxicity, or another withdrawal criteria is met.

  Interventions:

  • Drug: cetuximab
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: 5-fluorouracil
• Experimental: Safety Lead in

  Cycle 1:

  Week 1 - Cetuximab 400 mg/m2 on day 1; Cisplatin 100 mg/m2 on day 1 or Carboplatin AUC 5 on day 1; 5-FU 1000 mg/m2 on days 1-4

  Week 2 - Cetuximab 250 mg/m2 on day 1

  Week 3 - Cetuximab 250 mg/m2 on day 1

  Cycle 2 - 6:

  Week 1 - Cetuximab 250 mg/m2 on day 1; Cisplatin 100 mg/m2 on day 1 or Carboplatin AUC 5 on day 1; 5-FU 1000 mg/m2 on days 1-4

  Week 2 - Cetuximab 250 mg/m2 on day 1

  Week 3 - Cetuximab 250 mg/m2 on day 1

  After 6 cycles, patients may then receive weekly Cetuximab monotherapy 250 mg/m2 until progression of disease, unacceptable toxicity, or another withdrawal criteria is met.

  Interventions:

  • Drug: cetuximab
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: 5-fluorouracil

Inclusion Criteria:

• Head and neck cancer that was confirmed by tissue or cell biopsy
• Disease not suitable for local therapy
• Measurable or evaluable disease
• Karnofsky performance status(KPS)score of at least 70
• Organs are functioning well (bone marrow reserve, liver and kidney)
• Life expectancy of at least 12 weeks
• Signed informed consent document

Exclusion Criteria:

• Receiving another investigational medication within the last 30 days
• Prior chemotherapy, except if given as part of a multimodal treatment for locally advanced head and neck cancer that was completed more than 4 months prior to study entry.
• Nasopharyngeal carcinoma
• Previous treatment with monoclonal antibody therapy or other signal transduction inhibitors or EGFR targeting therapy except for prior cetuximab treatment given as part of a multimodal treatment for locally advanced head and neck cancer that was completed more than 4 months prior to study entry.
• Uncontrolled high blood pressure
• Heart disease or had a heart attack within the last year
• Currently have an infection that requires for you to take an IV antibiotic
• Currently receiving other therapies for your cancer, such as chemotherapy, radiation therapy, immunotherapy, and hormonal therapy
• Medical or psychological condition that would not permit the patient to complete the study or sign informed consent
• Known drug abuse (with the exception of alcohol abuse)
• Known allergic reaction against any of the components of the study treatment
• Second primary malignancy that is clinically detectable at the time of consideration for study enrollment
• Have had another type of cancer within the last 2 years
• You are currently pregnant or breastfeeding
• You are considering becoming pregnant or fathering a child