Study of IMC-1121B in Patients With Tumors That Have Not Responded to Therapy

Advanced Solid Tumors Clinical Trial

Official title:

Phase I Study of Weekly Anti-Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) Monoclonal Antibody IMC-1121B in Patients With Advanced Solid Tumors Who Have Not Responded to Standard Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00793975
• Other study ID #: 13918
• Secondary ID: CP12-0401I4T-IE-
• Status: Completed
• Phase: Phase 1
• First received: November 14, 2008
• Last updated: August 16, 2013
• Start date: January 2005
• Est. completion date: June 2009

Study information

• Verified date: August 2013
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if IMC-1121B is safe for patients, and to determine the best dose of IMC-1121B to give to patients.

Description:

The purpose of this study is to establish the safety profile and the maximum tolerated dose (MTD) of the anti-VEGFR-2 monoclonal antibody IMC-1121B administered weekly in patients with advanced solid tumors who have not responded to standard therapy or for whom no standard therapy is available.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histopathologically-documented, measurable or evaluable (non-measurable), advanced primary or recurrent solid tumors who have not responded to standard therapy or for whom no standard therapy is available.

• ECOG performance status score of = 2 at study entry

• Able to provide written informed consent

• A life expectancy of > 3 months

• Adequate hematologic function, as defined by: ANC = 1500/mm^3, hemoglobin level = 10 gm/dL, platelet count = 100,000/mm^3

• Adequate hepatic function, as defined by: total bilirubin level = 1.5 x the ULN, AST and ALT levels = 2.5 x the ULN or = 5 x the ULN if known liver metastases

• Adequate renal function, as defined by a serum creatinine level = 1.5 x the ULN

• Use of effective contraception (per the institutional standard), if procreative potential exists

• Adequate recovery from recent surgery, chemotherapy, and radiation therapy. At least 28 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy (palliative radiation therapy is allowed).

• Accessible for treatment and follow-up. Patients enrolled in this trial must be treated at the participating center.

Exclusion Criteria:

• Patients with large centrally-located pulmonary lesions adjacent to or invading large blood vessels.

• Patients who have had chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or patients with ongoing side effects = grade 2 due to agents administered more than 28 days earlier.

• Prior left chest wall radiotherapy or a cumulative anthracycline dose = 300mg/m2 (if the ejection fraction is within normal institutional limits, the patient can be enrolled).

• 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 = 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, unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months, uncontrolled hypertension, clinically significant cardiac arrhythmia, uncontrolled diabetes, psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements, patients with symptomatic brain metastases

• A serious or nonhealing active wound, ulcer, or bone fracture

• Known HIV positivity

• A major surgical procedure, an open biopsy, or a significant injury within 28 days prior to treatment

• Current or recent use (within 28 days) of a thrombolytic agent

• Current or recent use (within 28 days) of full-dose warfarin

• Chronic daily treatment with aspirin (>325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function

• History or clinical evidence of a deep venous or arterial thrombosis (including pulmonary embolism) within 6 months prior to study entry

• Proteinuria =1+ by routine urinalysis (patients with a protein value of = 500mg confirmed by a 24-hour urine collection are eligible)

• Pregnant (confirmed by serum beta human chorionic gonadotropin [ßHCG]) or breast feeding

• Prior treatment with bevacizumab or other agents specifically targeting VEGF ligand or receptor within 6 weeks of study entry

• Monoclonal antibodies within 6 weeks of study entry

• Positive anti-IMC-1121B antibody response

• 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 the employees.

Study Design

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

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Biological:
• IMC-1121B
Cohort 1 2 mg/kg I.V. once a week for 4 weeks, followed by a 2-week observation period.
• 1121B
Cohort 2 4 mg/kg I.V. once a week for 4 weeks, followed by a 2-week observation period.
• 1121B
Cohort 3 6 mg/kg I.V. once a week for 4 weeks, followed by a 2-week observation period.
• 1121B
Cohort 4 8 mg/kg I.V. once a week for 4 weeks, followed by a 2-week observation period.
• 1121B
Cohort 5 10 mg/kg I.V. once a week for 4 weeks, followed by a 2-week observation period.
• 1121B
Cohort 6 13 mg/kg once a week for 4 weeks, followed by a 2-week observation period.
• 1121B
Cohort 7 16 mg/kg once a week for 4 weeks, followed by a 2-week observation period.

Locations

Country	Name	City	State
United States	ImClone Investigational Site	Aurora	Colorado
United States	ImClone Investigational Site	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events (AEs)		6 weeks	Yes
Primary	Maximum Tolerated Dose		6 weeks	No
Secondary	Maximum concentration (Cmax), cohorts 1, 2, 3, 4, 5, 6. and 7		6 weeks	No
Secondary	Minimum concentration (Cmin), cohorts 1, 2, 3, 4, 5, 6. and 7		6 weeks	No
Secondary	Area under concentration (AUC), cohorts 1, 2, 3, 4, 5, 6. and 7		6 weeks	No
Secondary	Half-life (t 1/2), cohorts 1, 2, 3, 4, 5, 6. and 7		6 weeks	No
Secondary	Clearance (Cl) rate drug is completely removed, cohorts 1, 2, 3, 4, 5, 6. and 7		6 weeks	No
Secondary	Volume of distribution (Vss) at steady state, cohorts 1, 2, 3, 4, 5, 6. and 7		6 weeks	No
Secondary	Serum Anti-IMC-1121B Antibody Assessment (immunogenicity)		6 weeks	No
Secondary	Change in tumor size from Baseline Measurement		6 weeks	No