Study of IMC-11F8 in Patients With Tumors Who Have Not Responded to Standard Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine if IMC-11F8 is safe for patients, and also to determine the best dose of IMC-11F8 to give to patients.

Detailed Description
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The purpose of this study is to establish the safety profile and the maximum tolerated dose (MTD) of the fully human anti-EGFR monoclonal antibody IMC-11F8 in patients with solid tumors who have filed standard therapy or for whom no standard therapy is available.

Official Title
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Phase I Study of the Fully Human Anti-Epidermal Growth Factor Receptor (EGFR) Monoclonal Antibody IMC-11F8 in Patients With Solid Tumors Who Have Failed Standard Therapy

Conditions
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Solid Tumors

Intervention / Treatment
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* Biological: IMC-11F8
* Biological: IMC-11F8
* Biological: IMC-11F8
* Biological: IMC-11F8 I.V.
* Biological: IMC-11F8
* Biological: IMC-11F8
* Biological: IMC-11F8
* Biological: IMC-11F8
* Biological: IMC-11F8
* Biological: IMC-11F8
* Biological: IMC-11F8
* Biological: IMC-11F8


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-confirmed, EGFR-detectable or EGFR-undetectable, unidimensionally-measurable and/or evaluable solid tumors who failed standard therapy or for whom no standard therapy is available. Patients who do not have tissue available for EGFR testing will undergo a biopsy of an accessible tumor. ECOG performance status score of ≤ 2 at study entry. Able to provide written informed consent. White blood cell (WBC) count ≥ 3 x 109/L; an absolute neutrophil count ≥ 1.5 x 109/L; a hemoglobin level > 90 g/L; and a platelet count ≥ 100 x 109/L. Adequate hepatic function as defined by: an alkaline phosphatase level ≤ 5.0 x the ULN a bilirubin level ≤ 1.5 x the ULN aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2.5 x the ULN or ≤ 5 x the ULN for patients with liver metastases Adequate renal function as defined by a serum creatinine level within normal limits. Use of effective contraception if procreative potential exists. Life expectancy of approximately 3 months in the opinion the opinion of the investigator. Exclusion Criteria: Chemotherapy, radiation, and/or hormonal therapy (except palliative radiation therapy for disease-related pain and chronic hormonal therapy for prostate carcinoma) within 4 weeks of study entry. Concurrent unstable or uncontrolled medical disease (e.g., active uncontrolled systemic infection, poorly controlled hypertension or history of poor compliance with an anti-hypertensive regimen, unstable angina, congestive heart failure, uncontrolled diabetes) or other chronic disease, which, in the opinion of the investigator, could compromise the patient or the study. Newly-diagnosed or symptomatic brain metastases (patients with a history of brain metastases must have received definitive surgery or radiotherapy, be clinically stable, and not taking steroids; anticonvulsants are allowed). Any concurrent malignancy other than basal cell carcinoma 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. Any condition that prevents the patient from providing informed consent. Pregnancy (confirmed by serum beta human chorionic gonadotropin [ßHCG]) or breast-feeding. Any investigational agent(s) or device(s) within 4 weeks of study entry. Prior treatment with cetuximab, or any other epidermal growth factor receptor inhibitors, including tyrosine kinase inhibitors, such as gefitinib or erlotinib. Prior treatment with other monoclonal antibodies targeting receptors other than the EGFR is permitted ≥ 4 weeks prior to study entry. Any prior therapy that targeted the EGFR or EGFR pathway. Known history of human immunodeficiency virus. 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

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMC-11F8 (Every week)<br>Cycle of therapy administered intravenously, once a week for 6 weeks, for a total of six doses per cycle. | Biological: IMC-11F8<br>* Cohort 1 100 mg I.V.<br>* Other names: necitumumab;Biological: IMC-11F8<br>* Cohort 2 200 mg I.V.<br>* Other names: necitumumab;Biological: IMC-11F8<br>* Cohort 3 400 mg I.V.<br>* Other names: necitumumab;Biological: IMC-11F8 I.V.<br>* Cohort 4 600 mg I.V.<br>* Other names: necitumumab;Biological: IMC-11F8<br>* Cohort 5 800 mg I.V.<br>* Other names: necitumumab;Biological: IMC-11F8<br>* Cohort 6 1000 mg I.V.<br>* Other names: necitumumab;|
| Experimental: IMC-11F8 (Every other week)<br>Cycle of therapy administered intravenously, every other week for 6 weeks, for a total of three doses per cycle. | Biological: IMC-11F8<br>* Cohort 1 100 mg I.V.<br>* Other names: necitumumab;Biological: IMC-11F8<br>* Cohort 2 200 mg I.V.<br>* Other names: necitumumab;Biological: IMC-11F8<br>* Cohort 3 400 mg I.V.<br>* Other names: necitumumab;Biological: IMC-11F8<br>* Cohort 4 600 mg I.V.<br>* Other names: necitumumab;Biological: IMC-11F8<br>* Cohort 5 800 mg I.V.<br>* Other names: necitumumab;Biological: IMC-11F8<br>* Cohort 6 1000 mg I.V.<br>* Other names: necitumumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events |  | Approximately 24 Months | 
| Maximum Tolerated Dose of IMC-11F8 |  | Approximately 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the Time Concentration Curve (AUC) |  | Approximately 24 Months | 
| Maximum concentration (Cmax) |  | Approximately 24 Months | 
| Half-life (t 1/2) |  | Approximately 24 Months | 
| Serum Anti-IMC-11F8 Antibody Assessment |  | Approximately 24 Months | 
| Change from baseline in Antitumor Activity |  | Approximately 24 Months | 

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