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

Study Overview
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Brief Summary
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The purpose of this study is to determine if IMC-A12 alone or in combination with Cetuximab (Erbitux®) can increase the time prior to disease progression in participants with Squamous Cell Head and Neck Cancer who have had disease progression and platinum-containing chemotherapeutic regimen.

Detailed Description
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The routine cancer treatments for Squamous Cell Carcinoma Head and Neck Cancer have improved but still leave a percentage of participants with incurable disease. New alternatives for participants whose disease is refractory to existing therapies is needed. IMC-A12 is a monoclonal antibody which binds to special receptors known as insulin-like growth factor-I receptor (IGF-IR). 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 evaluate the effects of IMC-A12 by itself or with Cetuximab (Erbitux®) in participants 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 participant is receiving treatment.

Official Title
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A Randomized Phase 2 Open-Label Study of IMC-A12, as a Single Agent or in Combination With Cetuximab, in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck and Disease Progression on Prior Platinum-Based Chemotherapy

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: IMC-A12 (cixutumumab)
* Biological: cetuximab (Erbitux ®)


Participation Criteria
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Eligibility Criteria
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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 centimeters (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-epidermal growth factor receptor (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 milligrams per deciliter (mg/dL) or below the upper limit of normal (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 insulin-like growth factor receptor (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. Participants 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMC-A12 (cixutumumab)<br> | Biological: IMC-A12 (cixutumumab)<br>* IMC-A12 10 milligrams per kilogram (mg/kg) over one hour every two weeks. A cycle is defined as four weeks of therapy. Participants will continue on study until evidence of progressive disease, or unacceptable toxicity develops.<br>* Other names: LY3012217;|
| Experimental: IMC-A12 (cixutumumab) + cetuximab<br> | Biological: IMC-A12 (cixutumumab)<br>* IMC-A12 10 milligrams per kilogram (mg/kg) over one hour every two weeks. A cycle is defined as four weeks of therapy. Participants will continue on study until evidence of progressive disease, or unacceptable toxicity develops.<br>* Other names: LY3012217;Biological: cetuximab (Erbitux ®)<br>* IMC-A12 10 mg/kg over one hour followed by cetuximab 500 milligrams per square meter (mg/m^2) over two hours. This sequence will be repeated every two weeks. Participants will continue on study until evidence of progressive disease or unacceptable toxicity develops.<br>* Other names: Erbitux®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS was defined as the interval from randomization until PD or death, whichever occurred first. Response was defined using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.0) criteria. PD was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. PFS was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death. | Baseline to measured PD (up to 27.66 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | ORR was defined as the percentage of participants achieving either CR or PR. Response was defined using RECIST, version 1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Percentage of participants is calculated as a total number of participants with CR or PR divided by the total number of participants treated then multiplied by 100. | Baseline to measured PD (up to 27.66 months) | 
| Percentage of Participants With PFS at 6 Months | PFS at 6 months was defined as the percentage of participants who have neither experienced PD nor died at 6 months after the date of randomization. Response was defined using RECIST, version 1.0 criteria. PD was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. Percentage of participants is calculated as the total number of participants with PFS at 6 months divided by the total number of participants treated then multiplied by 100. | 6 months | 
| Overall Survival (OS) | OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive, OS was censored at the date of last follow-up visit or at the date of last contact. | Baseline to date of death from any cause (up to 29.63 months) | 
| Duration of Response | The duration of CR or PR was defined as the time from first objective status assessment of CR or PR to the first time of PD or death. Response was defined using RECIST, version 1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Duration of response was censored on the date of last tumor assessment for participants who were alive and have no evidence of PD. | Date of first response to the date of PD or death due to any cause (up to 23.98 months) | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Deaths | TEAEs were defined as serious and other non-serious adverse events (AEs) that occurred or worsened after study treatment (regardless of causality). Data presented are the number of participants who experienced TEAEs including serious TEAEs, and deaths during the study including the 30-day follow-up. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events section of this report. | Baseline through study completion (up to 29.63 months) | 
| Blood And Tissue Biomarkers And Development of Serum Antibodies Against IMC-A12 and Cetuximab | No data for biomarkers and serum antibodies were collected due to lack of an appropriate validated assay. | Biomarkers [pre-dose, Cycle 1 (Day 15), (Cycle 2 (Day 1), and end of treatment]; Immunogenicity [pre-dose, prior to first infusion for Cycle 3, Cycle 5, and 30-day safety follow-up] | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous Cell Carcinoma in Head and Neck, Prior Platinum-based chemotherapy, Cetuximab, Erbitux, IMC-A12