Clinical trial NCT00785538: A Study of IMC-A12 in Participants With Tumors Who No Longer Respond to Treatment or For Whom No Treatment is Available
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Tumors
Antibodies, Monoclonal
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-11-05
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) or Deaths
timeFrame: Enrollment to study completion up to 215 weeks
measure: Maximum Tolerated Dose (MTD)
timeFrame: 6 weeks
Secondary outcomes:
measure: Maximum Concentration (Cmax) of IMC-A12 Following Multiple Doses
timeFrame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
measure: Observed Serum Concentration of IMC-A12 at 168 Hour Post End of Infusion Following Multiple Doses
timeFrame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
measure: Area Under the Serum Concentration Versus Time Curve of IMC-A12 During One Dosing Interval (AUCτ) Following Multiple Doses
timeFrame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
measure: Half-Life (t1/2) of IMC-A12 Following Multiple Doses
timeFrame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
measure: Clearance Rate of IMC-A12 at Steady State (CLss) Following Multiple Doses
timeFrame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
measure: Volume of Distribution of IMC-A12 at Steady State (Vss) Following Multiple Doses
timeFrame: Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
measure: Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity)
timeFrame: Before the last infusion of each treatment cycle
measure: Number of Participants With Best Overall Response
timeFrame: Enrollment to study completion up to 215 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: ImClone Investigational Site
state: Arizona
city: Detroit
country: United States
facility: ImClone Investigational Site
state: Michigan
city: Seattle
country: United States
facility: ImClone Investigational Site
state: Washington
Study officials:
affiliation: Eli Lilly and Company
name: 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
References:
citation: 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.