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

Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00801177
• Other study ID #: 14088
• Secondary ID: 2004-002072-42CP
• Status: Completed
• Phase: Phase 1
• First received: December 2, 2008
• Last updated: October 11, 2010
• Start date: November 2004
• Est. completion date: February 2007

Study information

• Verified date: October 2010
• Source: ImClone LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Biological:
• IMC-11F8
Cohort 1 100 mg I.V.
• IMC-11F8
Cohort 2 200 mg I.V.
• IMC-11F8
Cohort 3 400 mg I.V.
• IMC-11F8 I.V.
Cohort 4 600 mg I.V.
• IMC-11F8
Cohort 5 800 mg I.V.
• IMC-11F8
Cohort 6 1000 mg I.V.
• IMC-11F8
Cohort 1 100 mg I.V.
• IMC-11F8
Cohort 2 200 mg I.V.
• IMC-11F8
Cohort 3 400 mg I.V.
• IMC-11F8
Cohort 4 600 mg I.V.
• IMC-11F8
Cohort 5 800 mg I.V.
• IMC-11F8
Cohort 6 1000 mg I.V.

Locations

Country	Name	City	State
Netherlands	ImClone Investigational Site	Amsterdam
Netherlands	ImClone Investigational Site	Utrecht

Sponsors (1)

Lead Sponsor	Collaborator
ImClone LLC

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

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 a

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 pres

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events		Approximately 24 Months	Yes
Primary	Maximum Tolerated Dose of IMC-11F8		Approximately 24 Months	Yes
Secondary	Area under the Time Concentration Curve (AUC)		Approximately 24 Months	No
Secondary	Maximum concentration (Cmax)		Approximately 24 Months	No
Secondary	Half-life (t 1/2)		Approximately 24 Months	No
Secondary	Serum Anti-IMC-11F8 Antibody Assessment		Approximately 24 Months	No
Secondary	Change from baseline in Antitumor Activity		Approximately 24 Months	No