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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00793975
First received: November 14, 2008
Last updated: August 16, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Advanced Solid Tumors
Biological: IMC-1121B
Biological: 1121B
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Number of participants with Adverse Events (AEs) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • Maximum Tolerated Dose [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maximum concentration (Cmax), cohorts 1, 2, 3, 4, 5, 6. and 7 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Minimum concentration (Cmin), cohorts 1, 2, 3, 4, 5, 6. and 7 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Area under concentration (AUC), cohorts 1, 2, 3, 4, 5, 6. and 7 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Half-life (t 1/2), cohorts 1, 2, 3, 4, 5, 6. and 7 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Clearance (Cl) rate drug is completely removed, cohorts 1, 2, 3, 4, 5, 6. and 7 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Volume of distribution (Vss) at steady state, cohorts 1, 2, 3, 4, 5, 6. and 7 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Serum Anti-IMC-1121B Antibody Assessment (immunogenicity) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Change in tumor size from Baseline Measurement [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 37
Study Start Date: January 2005
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMC-1121B

All patients will receive intravenous infusions of IMC-1121B with the dose depending on which cohort they are enrolled into. A minimum of three patients will be enrolled in each cohort.

A completed patient will be either a patient who completes the 4-week treatment cycle and 2-week observation period (for a total of 6 weeks), or a patient who discontinues therapy for an IMC-1121B-related toxicity. Toxicity data for each cohort will be reviewed prior to dose escalation.

When all patients complete a cohort, dose escalation to the next cohort will occur.

Biological: IMC-1121B

Cohort 1

2 mg/kg I.V. once a week for 4 weeks, followed by a 2-week observation period.

Biological: 1121B

Cohort 2

4 mg/kg I.V. once a week for 4 weeks, followed by a 2-week observation period.

Biological: 1121B

Cohort 3

6 mg/kg I.V. once a week for 4 weeks, followed by a 2-week observation period.

Biological: 1121B

Cohort 4

8 mg/kg I.V. once a week for 4 weeks, followed by a 2-week observation period.

Biological: 1121B

Cohort 5

10 mg/kg I.V. once a week for 4 weeks, followed by a 2-week observation period.

Biological: 1121B

Cohort 6

13 mg/kg once a week for 4 weeks, followed by a 2-week observation period.

Biological: 1121B

Cohort 7

16 mg/kg once a week for 4 weeks, followed by a 2-week observation period.


Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 [βHCG]) 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00793975

Locations
United States, Colorado
ImClone Investigational Site
Aurora, Colorado, United States, 80045
United States, Pennsylvania
ImClone Investigational Site
Philadelphia, Pennsylvania, United States, 19111
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Chair: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00793975     History of Changes
Other Study ID Numbers: 13918, CP12-0401, I4T-IE-JVBM
Study First Received: November 14, 2008
Last Updated: August 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Tumors
Antibodies, Monoclonal

Additional relevant MeSH terms:
Antibodies, Monoclonal
Endothelial Growth Factors
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Growth Substances

ClinicalTrials.gov processed this record on July 31, 2014