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Study of Anti-Vascular Endothelial Growth Factor Receptor Monoclonal Antibody in Patients With Advanced Solid Tumors Not Responding To Standard Therapy
This study is ongoing, but not recruiting participants.
Sponsored by: ImClone Systems
Information provided by: ImClone Systems
ClinicalTrials.gov Identifier: NCT00786383
  Purpose

We are conducting a research study for tumors that have not responded to prior treatment. The subject will receive an investigational drug called IMC-1121B. ImClone Systems Incorporated, the maker of IMC-1121B, is running this research study.

We believe that IMC-1121B blocks the growth factors made by the cancer cells, so new blood vessels do not grow. It is believed that without the new blood vessels, the cancer or tumor will not get the oxygen and food that it needs to grow. This may stop the cancer from growing or spreading and the tumor cells may die. Since normal blood vessels have already formed in adults, it might be possible to stop tumor growth without harming normal cells.


Condition Intervention Phase
Cancer
Biological: IMC-1121B
Phase I

MedlinePlus related topics: Cancer
Drug Information available for: Immunoglobulins Globulin, Immune
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Active Control, Single Group Assignment, Safety Study
Official Title: Phase 1 Study of Every Other Week 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

Further study details as provided by ImClone Systems:

Primary Outcome Measures:
  • Establish the safety profile and the maximum tolerated dose (MTD) [ Time Frame: 8 Weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • pharmacokinetics [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
  • Immunogenicity [ Time Frame: 8 Weeks ] [ Designated as safety issue: Yes ]
  • antitumor activity [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: January 2006
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
IMC-1121B injectable solution at a concentration of 5 mg/mL in single-use vials containing 100 mg/20 mL or 250 mg/50 mL of product, administered intravenously at an initial dose of 6 mg/kg.
Biological: IMC-1121B
IMC-1121B, administered intravenously, once every other week the starting dose will be 6 mg/kg in cohort 1.(cohorts 1 through 3) or once every 3 weeks intravenously, once every 3 weeks on day 1 of each treatment cycle, for a total of one dose per cycle. Patients will receive 15 mg/kg and 20 mg/kg in cohorts 4 and 5, respectively.(cohorts 4 and 5).

Detailed Description:

We are conducting a research study for tumors that have not responded to prior treatment. The subject will receive an investigational drug called IMC-1121B. ImClone Systems Incorporated, the maker of IMC-1121B, is running this research study.

In order for a cancer to grow, it needs blood vessels to bring to it oxygen and food. Cancer cells can make growth factors that cause the abnormal growth of new blood vessels. This is called angiogenesis. Normally, new blood vessels do not grow in adults. Angiogenesis inhibitors are drugs that may prevent abnormal growth of blood vessels to tumors. IMC-1121B is an angiogenesis inhibitor. We believe that IMC-1121B blocks the growth factors made by the cancer cells, so new blood vessels do not grow. It is believed that without the new blood vessels, the cancer or tumor will not get the oxygen and food that it needs to grow. This may stop the cancer from growing or spreading and the tumor cells may die. Since normal blood vessels have already formed in adults, it might be possible to stop tumor growth without harming normal cells.

  Eligibility

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

Inclusion Criteria:

  • Patients with 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
  • Eastern Cooperative Oncology Group (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:

    • an absolute neutrophil count ≥1500/mm3
    • a hemoglobin level ≥10 gm/dL
    • a platelet count ≥100,000/mm3
  • Adequate hepatic function, as defined by:

    • a total bilirubin level ≤1.5 x the upper limit of normal (ULN)
    • aspartate transaminase (AST) and alanine transaminase (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 , 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
  • 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 ≥300 mg/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 for ≥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 (class III or IV of the New York Heart Association classification for heart disease)
    • unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
    • uncontrolled hypertension (systolic blood pressure ≥160 mm Hg, diastolic blood pressure >100 mm Hg, found on two consecutive measurements separated by a 1-week period despite adequate medical support)
    • clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment or asymptomatic sustained ventricular tachycardia)
    • uncontrolled diabetes
    • psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements
    • patients with 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)
  • A serious or nonhealing active wound, ulcer, or bone fracture.
  • Known human immunodeficiency-positivity.
  • A major surgical procedure, an open biopsy, or a significant traumatic 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 (an exception is low-dose warfarin to maintain patency of preexisting, permanent, indwelling intravenous (i.v.) catheters; for patients receiving warfarin, the international normalized ratio [INR] should be <1.5). Patients requiring heparin are excluded.
  • Chronic daily treatment with aspirin (>325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function (cyclooxygenase-2 [COX-2] inhibitors are permitted).
  • A history or clinical evidence of a deep venous or arterial thrombosis (including pulmonary embolism) within the last 6 months prior to study entry.
  • Proteinuria ≥1+ by routine urinalysis (patients with a protein value of ≤500 mg 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.
  • A history of allergic reactions to monoclonal antibodies or other therapeutic proteins.
  • The subject is the investigator, sub-investigator, or anyone directly involved in the conduct of the protocol.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00786383

Locations
United States, Indiana
Indiana Cancer Pavilion
Indianapolis, Indiana, United States, 46202-5112
Sponsors and Collaborators
ImClone Systems
Investigators
Principal Investigator: Gabriela Chiorean, MD Indiana Cancer Pavilion
  More Information

Responsible Party: ImClone Systems Incorporated ( Eric Rowinsky/ Chief Medical Officer )
Study ID Numbers: CP12-0402
Study First Received: November 4, 2008
Last Updated: November 5, 2008
ClinicalTrials.gov Identifier: NCT00786383  
Health Authority: United States: Food and Drug Administration

Keywords provided by ImClone Systems:
Phase I
cancer
solid tumors
1121B
VEGFR-2
Anti-Vascular Endothelial Growth Factor Receptor 2

Study placed in the following topic categories:
Antibodies, Monoclonal
Antibodies
Endothelial Growth Factors
Immunoglobulins

Additional relevant MeSH terms:
Immunologic Factors
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009