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

• ClinicalTrials.gov Identifier: NCT00801177
• Recruitment Status: Completed
• First Posted: December 3, 2008
• Last Update Posted: October 13, 2010
• Sponsor: Eli Lilly and Company
• Information provided by: Eli Lilly and Company

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Solid Tumors	Biological: IMC-11F8; Biological: IMC-11F8 I.V.	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• 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 Start Date: November 2004
• Actual Primary Completion Date: February 2007
• Actual Study Completion Date: February 2007

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with Adverse Events [ Time Frame: Approximately 24 Months ]
2. Maximum Tolerated Dose of IMC-11F8 [ Time Frame: Approximately 24 Months ]

Secondary Outcome Measures :

1. Area under the Time Concentration Curve (AUC) [ Time Frame: Approximately 24 Months ]
2. Maximum concentration (Cmax) [ Time Frame: Approximately 24 Months ]
3. Half-life (t 1/2) [ Time Frame: Approximately 24 Months ]
4. Serum Anti-IMC-11F8 Antibody Assessment [ Time Frame: Approximately 24 Months ]
5. Change from baseline in Antitumor Activity [ Time Frame: Approximately 24 Months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Netherlands

ImClone Investigational Site

Amsterdam, Netherlands, 1081 HV

ImClone Investigational Site

Utrecht, Netherlands, 3508 GA

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Chair: E-mail: ClinicalTrials@ ImClone.com; Eli Lilly and Company

More Information

Publications of Results:

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.

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.

• Responsible Party: Chief Medical Officer, ImClone LLC
• ClinicalTrials.gov Identifier: NCT00801177
• Other Study ID Numbers: 14088; 2004-002072-42 ( EudraCT Number ); CP11-0401 ( Other Identifier: ImClone, LLC )
• First Posted: December 3, 2008
• Last Update Posted: October 13, 2010
• Last Verified: October 2010

Keywords provided by Eli Lilly and Company:

Tumors; Antibodies, Monoclonal

Additional relevant MeSH terms:

Neoplasms; Necitumumab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs