Clinical trial NCT00785941: A Study of IMC-A12 Every 2 Weeks in Patients With Tumors Who No Longer Respond to Treatment or No Treatment is Available
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
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: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: 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.

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 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

Primary outcomes:
measure: Number of participants with Adverse Events (AEs)
timeFrame: 8 weeks
measure: Maximum Tolerated Dose
timeFrame: 8 weeks
Secondary outcomes:
measure: Maximum concentration (Cmax), cohorts 1, 2, 3, 4, and 5
timeFrame: 8 weeks
measure: Minimum concentration (Cmin), cohorts 1, 2, 3, 4, and 5
timeFrame: 8 weeks
measure: Area under concentration (AUC), cohorts 1, 2, 3, 4, and 5
timeFrame: 8 weeks
measure: Half-life (t 1/2), cohorts 1, 2, 3, 4, and 5
timeFrame: 8 weeks
measure: Clearance (Cl) rate drug is completely removed, cohorts 1, 2, 3, 4, and 5
timeFrame: 8 weeks
measure: Volume of distribution (Vss) at steady state, cohorts 1, 2, 3, 4, and 5
timeFrame: 8 weeks
measure: Serum Anti-IMC-A12 Antibody Assessment (immunogenicity)
timeFrame: 8 weeks
measure: Change in tumor size from Baseline Measurement
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Nashville
country: United States
facility: ImClone Investigational Site
state: Tennessee
Study officials:
affiliation: Eli Lilly and Company
name: E-mail: ClinicalTrials@ ImClone.com
role: STUDY_CHAIR
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.