A Study of IMC-A12 in Participants With Tumors Who No Longer Respond to Treatment or For Whom No Treatment is Available

NCT ID: NCT00785538

Last Updated: 2019-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31
• Study Completion Date: 2011-01-31

Brief Summary

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

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 participants with advanced solid tumors who no longer respond to standard therapy or for whom no standard therapy is available

Conditions

Advanced Solid Tumors

Study Design

• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IMC-A12

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

Group Type: EXPERIMENTAL

IMC-A12

Intervention Type: BIOLOGICAL

Cohort 1

3 milligrams/kilogram (mg/kg), I.V. once a week, for 4 weeks, followed by a 2-week observation period.

IMC-A12

Intervention Type: BIOLOGICAL

Cohort 2

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

IMC-A12

Intervention Type: BIOLOGICAL

Cohort 3

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

IMC-A12

Intervention Type: BIOLOGICAL

Cohort 4

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

IMC-A12

Intervention Type: BIOLOGICAL

Cohort 5

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

IMC-A12

Intervention Type: BIOLOGICAL

Cohort 6

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

Interventions

IMC-A12

Cohort 1

3 milligrams/kilogram (mg/kg), I.V. once a week, for 4 weeks, followed by a 2-week observation period.

Intervention Type: BIOLOGICAL

IMC-A12

Cohort 2

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

Intervention Type: BIOLOGICAL

IMC-A12

Cohort 3

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

Intervention Type: BIOLOGICAL

IMC-A12

Cohort 4

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

Intervention Type: BIOLOGICAL

IMC-A12

Cohort 5

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

Intervention Type: BIOLOGICAL

IMC-A12

Cohort 6

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Cixutumumab; LY3012217; Cixutumumab; LY3012217; Cixutumumab; LY3012217; Cixutumumab; LY3012217; Cixutumumab; LY3012217; Cixutumumab; LY3012217

Eligibility Criteria

Inclusion Criteria

• Histopathologically-documented, measurable, advanced primary or recurrent solid tumors that no longer respond to standard therapy or for which no standard therapy is available.
• Eastern Cooperative Oncology Group (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: absolute neutrophil count (ANC) ≥1500/cubic millimeter (mm³), hemoglobin level ≥10 grams/deciliter (gm/dL), platelet count ≥100,000/mm³
• Adequate hepatic function, as defined by: 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
• 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 insulin-like growth factor receptor (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. Participants 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. Participants 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 participant safety or limit compliance with study requirements, participants with symptomatic brain metastases
• Serious or nonhealing active wound, ulcer or bone fracture
• Know human immunodeficiency virus (HIV)-positive
• History of hemorrhagic or thrombotic disorder within 9 months
• Proteinuria ≥1+ by routine urinalysis (participants with a protein value of ≤500 milligrams (mg) 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

ImClone Investigational Site

Scottsdale, Arizona, United States

ImClone Investigational Site

Detroit, Michigan, United States

ImClone Investigational Site

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 25749986 (View on PubMed)

Other Identifiers

CP13-0501

Identifier Type: OTHER

Identifier Source: secondary_id

I5A-IE-JAEH

Identifier Type: OTHER

Identifier Source: secondary_id

13932

Identifier Type: -

Identifier Source: org_study_id