Clinical trial NCT00801177: Study of IMC-11F8 in Patients With Tumors Who Have Not Responded to Standard Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Tumors
Antibodies, Monoclonal
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-12-03
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Adverse Events
timeFrame: Approximately 24 Months
measure: Maximum Tolerated Dose of IMC-11F8
timeFrame: Approximately 24 Months
Secondary outcomes:
measure: Area under the Time Concentration Curve (AUC)
timeFrame: Approximately 24 Months
measure: Maximum concentration (Cmax)
timeFrame: Approximately 24 Months
measure: Half-life (t 1/2)
timeFrame: Approximately 24 Months
measure: Serum Anti-IMC-11F8 Antibody Assessment
timeFrame: Approximately 24 Months
measure: Change from baseline in Antitumor Activity
timeFrame: Approximately 24 Months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: ImClone Investigational Site
city: Utrecht
country: Netherlands
facility: ImClone Investigational Site
Study officials:
affiliation: Eli Lilly and Company
name: E-mail: ClinicalTrials@ ImClone.com
role: STUDY_CHAIR
References:
citation: Kuenen B, Witteveen E, Ruijter R, Ervin-Haynes A, Tjin-A-ton M, Fox F, et al. A phase I study of IMC-11F8, a fully human anti-epidermal growth factor receptor (EGFR) IgG1 monoclonal antibody in patients with solid tumors. Interim results. [abstract 3024 and poster presentation]. American Society of Clinical Oncology Annual Meeting. 2006 June 2-6; Atlanta, GA.
citation: Kuenen B, Witteveen PO, Ruijter R, Tjin-A-Ton M, Youssoufian H, Rowinsky E, et al. A phase I study of IMC-11F8, a recombinant human anti-epidermal growth factor receptor IgG1 monoclonal antibody in patients with solid tumors. [abstract B52 and poster presentaton] International Conference on Molecular Targets and Cancer Therapeutics 2007 Oct 22-26; San Francisco, CA.