A Study of IMC-A12 Every 2 Weeks in Patients With Tumors Who No Longer Respond to Treatment or No Treatment is Available

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ImClone LLC
ClinicalTrials.gov Identifier:
NCT00785941
First received: November 4, 2008
Last updated: October 12, 2011
Last verified: October 2011
  Purpose

The purpose of this study is to determine if IMC-A12 is safe for patients, and also to determine the best dose of IMC-A12 to give to patients.


Condition Intervention Phase
Advanced Solid Tumors
Biological: IMC-A12
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Phase I Study of Anti-Insulin-Like Growth Factor-I Receptor (IGF-IR) Monoclonal Antibody IMC-A12 Administered Every Other Week in Patients With Advanced Solid Tumors Who No Longer Respond to Standard Therapy or for Whom No Standard Therapy is Available

Resource links provided by NLM:


Further study details as provided by ImClone LLC:

Primary Outcome Measures:
  • Number of participants with Adverse Events (AEs) [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Maximum Tolerated Dose [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maximum concentration (Cmax), cohorts 1, 2, 3, 4, and 5 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Minimum concentration (Cmin), cohorts 1, 2, 3, 4, and 5 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Area under concentration (AUC), cohorts 1, 2, 3, 4, and 5 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Half-life (t 1/2), cohorts 1, 2, 3, 4, and 5 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Clearance (Cl) rate drug is completely removed, cohorts 1, 2, 3, 4, and 5 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Volume of distribution (Vss) at steady state, cohorts 1, 2, 3, 4, and 5 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Serum Anti-IMC-A12 Antibody Assessment (immunogenicity) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in tumor size from Baseline Measurement [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: April 2006
Study Completion Date: November 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMC-A12

All patients will receive intravenous infusions of IMC-A12, with the dose depending on which cohort they are enrolled into a minimum of three patients will be enrolled in each Cohort. When all patients complete a cohort, dose escalation to the next Cohort will occur.

A treatment cycle will consist of IMC-A12 administered intravenously, once every other week for 4 weeks, for a total of 2 doses; followed by a 2-week observation period.

Biological: IMC-A12

Cohort 1

6 mg/kg I.V., once every other week for 4 weeks

Other Name: Cixutumumab
Biological: IMC-A12

Cohort 2

10 mg/kg I.V., once every other week for 4 weeks

Other Name: Cixutumumab
Biological: IMC-A12

Cohort 3

15 mg/kg I.V., once every other week for 4 weeks

Other Name: Cixutumumab
Biological: IMC-A12

Cohort 4

21 mg/kg I.V., once every other week for 4 weeks

Other Name: Cixutumumab
Biological: IMC-A12

Cohort 5

27 mg/kg I.V., once every other week for 4 weeks

Other Name: Cixutumumab

Detailed Description:

The purpose of this study is to establish the safety profile and maximum tolerated dose (MTD) of the anti-IGF-IR monoclonal antibody IMC-A12 administered every other week in patients with advanced solid tumors who no longer respond 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

  • Patients with histopathologically-documented, measurable, advanced primary or recurrent solid tumors who no longer respond to standard therapy or for whom no standard therapy is available
  • A life expectancy of >3 months
  • Adequate hematologic function
  • Adequate hepatic function
  • Adequate renal function
  • Use of effective contraception, if procreative potential exists.
  • At least 28 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, prior radiation therapy (palliative radiation therapy is allowed), an open biopsy, or a significant traumatic injury to allow for adequate recovery
  • At least 6 weeks must have elapsed from nitrosoureas, mitomycin C, or monoclonal antibody therapy to allow for adequate recovery
  • Accessible for treatment and follow-up. Patients enrolled in this trial must be treated at the participating center

Exclusion Criteria

  • 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 [National Cancer Institute {NCI}-Common Terminology Criteria for Adverse Events {CTCAE}, Version 3.0, grade 3] or asymptomatic sustained ventricular tachycardia)
    • 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 be clinically stable and not taking steroids; anticonvulsants are allowed)
  • A serious or nonhealing active wound, ulcer, or bone fracture
  • Known human immunodeficiency virus-positive
  • A history of a hemorrhagic or thrombotic disorder within 9 months
  • Pregnant or breast feeding
  • A history of prior treatment with other agents specifically targeting IGFRs.
  • Known diabetes
  • Inability or unwillingness to interrupt steroidal or hormonal therapy for the duration of treatment with IMC-A12
  • A positive anti-IMC-A12 antibody response
  • A 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 of the employees
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00785941

Locations
United States, Tennessee
ImClone Investigational Site
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
ImClone LLC
Investigators
Study Chair: E-mail: ClinicalTrials@ ImClone.com ImClone LLC
  More Information

No publications provided

Responsible Party: ImClone LLC
ClinicalTrials.gov Identifier: NCT00785941     History of Changes
Other Study ID Numbers: 13933, CP13-0502, I5A-IE-JAEI
Study First Received: November 4, 2008
Last Updated: October 12, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by ImClone LLC:
Tumors
Antibodies, Monoclonal

ClinicalTrials.gov processed this record on April 17, 2014