A Study of IMC-A12 in Patients With Tumors Who No Longer Respond to Treatment or Who No Treatment if Available

This study has been completed.
Sponsor:
Information provided by:
ImClone LLC
ClinicalTrials.gov Identifier:
NCT00785538
First received: November 4, 2008
Last updated: June 14, 2011
Last verified: June 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: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Anti-Insulin-Like Growth Factor-I Receptor (IGF-IR) Monoclonal Antibody IMC-A12 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: 6 weeks ] [ Designated as safety issue: Yes ]
  • Maximum Tolerated Dose [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Maximum concentration (Cmax), cohorts 1, 2, 3, 4, 5, and 6 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Minimum concentration (Cmin), cohorts 1, 2, 3, 4, 5, and 6 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Area under concentration (AUC), cohorts 1, 2, 3, 4, 5, and 6 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Half-life (t 1/2), cohorts 1, 2, 3, 4, 5, and 6 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Clearance (Cl) rate drug is completely removed, cohorts 1, 2, 3, 4, 5, and 6 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Volume of distribution (Vss) at steady state, cohorts 1, 2, 3, 4, 5, and 6 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Serum Anti-IMC-A12 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: 24
Study Start Date: October 2005
Study Completion Date: January 2011
Primary Completion Date: January 2011 (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.
Biological: IMC-A12

Cohort 1

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

Biological: IMC-A12

Cohort 2

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

Biological: IMC-A12

Cohort 3

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

Biological: IMC-A12

Cohort 4

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

Biological: IMC-A12

Cohort 5

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

Biological: IMC-A12

Cohort 6

27 mg/kg, I.V. 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 maximum tolerated dose (MTD) of the anti-IGF-IR monoclonal antibody IMC-A12 administered weekly 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:

  • Histopathologically-documented, measurable, advanced primary or recurrent solid tumors who no longer respond 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
  • Life expectancy of > 3 months
  • Adequate hematologic functions, as defined by: ANC ≥ 1500mm3, hemoglobin level ≥ 10 gm/dL, platelet count ≥ 100,000/mm3
  • 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
  • Ejection fraction within the normal institutional limits
  • Use of effective contraception per institutional standard, 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. Ongoing side effects due to these agents must be ≤ grade 2 prior to entering the study.
  • At least 6 weeks must have elapsed from nitrosoureas, mitomycin C, or monoclonal antibody (not targeting the IGFR) therapy to allow for adequate recovery. Ongoing side effects due to these agents must be ≤ grade 2 prior to entering the study.
  • 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, unstable angina pectoris, angioplasty, stenting or myocardial infarction within 6 months, uncontrolled hypertension, clinically significant cardiac arrhythmia, psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements, patients with symptomatic brain metastases
  • Serious or nonhealing active wound, ulcer or bone fracture
  • Know HIV-positive
  • History of hemorrhagic or thrombotic disorder within 9 months
  • 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
  • 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
  • Positive anti-IMC-A12 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 of 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: NCT00785538

Locations
United States, Arizona
ImClone Investigational Site
Scottsdale, Arizona, United States, 85258
United States, Michigan
ImClone Investigational Site
Detroit, Michigan, United States, 48201
United States, Washington
ImClone Investigational Site
Seattle, Washington, United States, 98109
Sponsors and Collaborators
ImClone LLC
Investigators
Study Chair: E-mail: ClinicalTrials@ ImClone.com ImClone LLC
  More Information

No publications provided

Responsible Party: Chief Medical Officer, ImClone LLC
ClinicalTrials.gov Identifier: NCT00785538     History of Changes
Other Study ID Numbers: 13932, CP13-0501, I5A-IE-JAEH
Study First Received: November 4, 2008
Last Updated: June 14, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by ImClone LLC:
Tumors
Antibodies, Monoclonal

ClinicalTrials.gov processed this record on July 24, 2014