A Study of IMC-A12 Every 2 Weeks in Patients With Tumors Who No Longer Respond to Treatment or No Treatment is Available

Study Overview
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Brief Summary
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The purpose of this study is to determine if IMC-A12 is safe for patients, and also to determine the best dose of IMC-A12 to give to patients.

Detailed Description
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The purpose of this study is to establish the safety profile and maximum tolerated dose (MTD) of the anti-IGF-IR monoclonal antibody IMC-A12 administered every other week in patients with advanced solid tumors who no longer respond to standard therapy or for whom no standard therapy is available.

Official Title
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Phase I Study of Anti-Insulin-Like Growth Factor-I Receptor (IGF-IR) Monoclonal Antibody IMC-A12 Administered Every Other Week in Patients With Advanced Solid Tumors Who No Longer Respond to Standard Therapy or for Whom No Standard Therapy is Available

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Biological: IMC-A12
* Biological: IMC-A12
* Biological: IMC-A12
* Biological: IMC-A12
* Biological: IMC-A12


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients with histopathologically-documented, measurable, advanced primary or recurrent solid tumors who no longer respond to standard therapy or for whom no standard therapy is available A life expectancy of >3 months Adequate hematologic function Adequate hepatic function Adequate renal function Use of effective contraception, if procreative potential exists. At least 28 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, prior radiation therapy (palliative radiation therapy is allowed), an open biopsy, or a significant traumatic injury to allow for adequate recovery At least 6 weeks must have elapsed from nitrosoureas, mitomycin C, or monoclonal antibody therapy to allow for adequate recovery Accessible for treatment and follow-up. Patients enrolled in this trial must be treated at the participating center Exclusion Criteria Any concurrent malignancy other than non-melanomatous skin cancer or carcinoma in situ of the cervix. Patients with a previous malignancy but without evidence of disease for ≥3 years will be allowed to enter the trial Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection requiring parenteral antibiotics symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease) unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months uncontrolled hypertension (systolic blood pressure >160 mm Hg, diastolic blood pressure >100 mm Hg, found on two consecutive measurements separated by a 1-week period despite adequate medical support) clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment [National Cancer Institute {NCI}-Common Terminology Criteria for Adverse Events {CTCAE}, Version 3.0, grade 3] or asymptomatic sustained ventricular tachycardia) psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements patients with symptomatic brain metastases (patients with a history of brain metastases must be clinically stable and not taking steroids; anticonvulsants are allowed) A serious or nonhealing active wound, ulcer, or bone fracture Known human immunodeficiency virus-positive A history of a hemorrhagic or thrombotic disorder within 9 months Pregnant or breast feeding A history of prior treatment with other agents specifically targeting IGFRs. Known diabetes Inability or unwillingness to interrupt steroidal or hormonal therapy for the duration of treatment with IMC-A12 A positive anti-IMC-A12 antibody response A history of allergic reactions to monoclonal antibodies or other therapeutic proteins Employees of the investigator or study center with direct involvement in this study or other studies under the direction of the investigator or study center, as well as family members of the employees

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

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMC-A12<br>All patients will receive intravenous infusions of IMC-A12, with the dose depending on which cohort they are enrolled into a minimum of three patients will be enrolled in each Cohort. When all patients complete a cohort, dose escalation to the next Cohort will occur. A treatment cycle will consist of IMC-A12 administered intravenously, once every other week for 4 weeks, for a total of 2 doses; followed by a 2-week observation period. | Biological: IMC-A12<br>* Cohort 1 6 mg/kg I.V., once every other week for 4 weeks<br>* Other names: Cixutumumab;Biological: IMC-A12<br>* Cohort 2 10 mg/kg I.V., once every other week for 4 weeks<br>* Other names: Cixutumumab;Biological: IMC-A12<br>* Cohort 3 15 mg/kg I.V., once every other week for 4 weeks<br>* Other names: Cixutumumab;Biological: IMC-A12<br>* Cohort 4 21 mg/kg I.V., once every other week for 4 weeks<br>* Other names: Cixutumumab;Biological: IMC-A12<br>* Cohort 5 27 mg/kg I.V., once every other week for 4 weeks<br>* Other names: Cixutumumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events (AEs) |  | 8 weeks | 
| Maximum Tolerated Dose |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax), cohorts 1, 2, 3, 4, and 5 |  | 8 weeks | 
| Minimum concentration (Cmin), cohorts 1, 2, 3, 4, and 5 |  | 8 weeks | 
| Area under concentration (AUC), cohorts 1, 2, 3, 4, and 5 |  | 8 weeks | 
| Half-life (t 1/2), cohorts 1, 2, 3, 4, and 5 |  | 8 weeks | 
| Clearance (Cl) rate drug is completely removed, cohorts 1, 2, 3, 4, and 5 |  | 8 weeks | 
| Volume of distribution (Vss) at steady state, cohorts 1, 2, 3, 4, and 5 |  | 8 weeks | 
| Serum Anti-IMC-A12 Antibody Assessment (immunogenicity) |  | 8 weeks | 
| Change in tumor size from Baseline Measurement |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tumors, Antibodies, Monoclonal