Study of IMC-A12, Alone or in Combination With Cetuximab, in Patients With Recurrent or Metastatic Squamous Cell Carcinoma (MSCC) of the Head and Neck

• Objective response rates (ORR) [ Time Frame: 6 months ]
  Evaluation every 6 month for PD or dies
• 6-month PFS rates [ Time Frame: 6 months ]
  6 Month Progression Free Survival (PFS) rate will be Determined every
• Overall survival rates [ Time Frame: 6 months ]
  Patients will be examined every 6 months to determine overall survival rate
• Duration of response [ Time Frame: 6 months ]
  Duration of response will be determined every 6 months.
• Summary Listing of Participants Reporting Treatment-Emergent Adverse Events [ Time Frame: 6 months ]
  Safety and AE-from 1st treatment every 2 weeks until 30 days post last treatment (therapy related AE followed until resolution or deemed irreversible
• Blood and tissue biomarkers and the development of serum antibodies against IMC-A12 and cetuximab [ Time Frame: 6 months ]
  Immunogenicity-Prior to 1st infusion, prior to Cycle 3 infusion, prior to cycle 5 infusion If infusion reaction to A12- closest to onset, at resolution and 30 days after event.

The routine cancer treatments for Squamous Cell Carcinoma Head and Neck Cancer have improved but still leave a percentage of patients with incurable disease. New alternatives for patients whose disease is refractory to existing therapies is needed.

IMC-A12 is a monoclonal antibody which binds to special receptors known as IGF-1R. This binding action has been shown to inhibit the growth of a variety of human tumor cell lines.

The purpose of this study is to evaluation the effects of IMC-A12 by itself or with Cetuximab (Erbitux®) in patients with Squamous Cell Carcinoma Head and Neck Cancer that has spread to other parts of the body, and to determine how long the drug remains in the body. The study will also look at what side effects IMC-A12 may cause when a patient is receiving treatment.

• Biological: IMC-A12 (cixutumumab)
  IMC-A12 10 mg/kg over one hour every two weeks. A cycle is defined as four weeks of therapy. Patients will continue on study until evidence of progressive disease, or unacceptable toxicity develops.
  Other Name: Cixutumumab
• Biological: cetuximab (Erbitux ®)
  IMC-A12 10 mg/kg over one hour followed by cetuximab 500 mg/m2 over 2 hours. This sequence will be repeated every 2 weeks. Patients will continue on study until evidence of disease progressive disease or unacceptable toxicity develops.
  Other Name: Erbitux®

• Experimental: IMC-A12 (cixutumumab)
  Intervention: Biological: IMC-A12 (cixutumumab)
• Experimental: IMC-A12 (cixutumumab) + cetuximab
  Interventions:

  • Biological: IMC-A12 (cixutumumab)
  • Biological: cetuximab (Erbitux ®)

Inclusion Criteria:

• Histologically or cytologically-confirmed squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity, metastasis or recurrence documented by clinical imaging studies
• Measurable disease, lesion size ≥ 2 cm on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan
• Clinical documentation of disease progression during treatment with or within 90 days after receiving the last cycle of platinum-based chemotherapy (with or without radiation therapy)
• If prior treatment with anti-EGFR therapy, the time to recurrence from last exposure to anti-EGFR therapy is > 90 days
• Adequate hematologic function
• Adequate hepatic function
• Adequate coagulation function or is on a stable dose of an anticoagulant.
• Adequate renal function
• Fasting serum glucose <120 mg/dL or below the ULN
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

Exclusion Criteria:

• Not recovered from adverse events due to agents administered more than 4 weeks earlier. Neurotoxicity, must have recovered to grade ≤ 2
• Is receiving any other investigational agent(s)
• History of treatment with other agents targeting the IGFR
• Is receiving concurrent treatment with other anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy
• History of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab or IMC-A12
• Has poorly controlled diabetes mellitus. Patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition
• Pregnant or breastfeeding
• Is receiving therapy with immunosuppressive agents