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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Biological: IMC-A12; Biological: IMC-A12; Biological: IMC-A12; Biological: IMC-A12; Biological: IMC-A12

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • ImClone Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: Cixutumumab; Biological: IMC-A12; Cohort 2 10 mg/kg I.V., once every other week for 4 weeks; Other Names: Cixutumumab; Biological: IMC-A12; Cohort 3 15 mg/kg I.V., once every other week for 4 weeks; Other Names: Cixutumumab; Biological: IMC-A12; Cohort 4 21 mg/kg I.V., once every other week for 4 weeks; Other Names: Cixutumumab; Biological: IMC-A12; Cohort 5 27 mg/kg I.V., once every other week for 4 weeks; Other Names: Cixutumumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with Adverse Events (AEs)	8 weeks
Maximum Tolerated Dose	8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum concentration (Cmax), cohorts 1, 2, 3, 4, and 5	8 weeks
Minimum concentration (Cmin), cohorts 1, 2, 3, 4, and 5	8 weeks
Area under concentration (AUC), cohorts 1, 2, 3, 4, and 5	8 weeks
Half-life (t 1/2), cohorts 1, 2, 3, 4, and 5	8 weeks
Clearance (Cl) rate drug is completely removed, cohorts 1, 2, 3, 4, and 5	8 weeks
Volume of distribution (Vss) at steady state, cohorts 1, 2, 3, 4, and 5	8 weeks
Serum Anti-IMC-A12 Antibody Assessment (immunogenicity)	8 weeks
Change in tumor size from Baseline Measurement	8 weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Higano CS, Berlin J, Gordon M, LoRusso P, Tang S, Dontabhaktuni A, Schwartz JD, Cosaert J, Mehnert JM. Safety, tolerability, and pharmacokinetics of single and multiple doses of intravenous cixutumumab (IMC-A12), an inhibitor of the insulin-like growth factor-I receptor, administered weekly or every 2 weeks in patients with advanced solid tumors. Invest New Drugs. 2015 Apr;33(2):450-62. doi: 10.1007/s10637-015-0217-7. Epub 2015 Mar 7.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: November 4, 2008
• First Submitted That Met QC Criteria: November 4, 2008
• First Posted (Estimate): November 5, 2008

Study Record Updates

• Last Update Posted (Estimate): October 13, 2011
• Last Update Submitted That Met QC Criteria: October 12, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Tumors; Antibodies, Monoclonal
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: 13933; CP13-0502 (Other Identifier: ImClone, LLC); I5A-IE-JAEI (Other Identifier: Eli Lilly and Company)