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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00785538
• Other study ID #: 13932
• Secondary ID: CP13-0501I5A-IE-
• Status: Completed
• Phase: Phase 1
• Start date: October 2005
• Est. completion date: January 2011

Study information

• Verified date: December 2018
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (ßHCG)] 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.

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Biological:
• IMC-A12
Cohort 1 3 milligrams/kilogram (mg/kg), I.V. once a week, for 4 weeks, followed by a 2-week observation period.
• IMC-A12
Cohort 2 6 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
• IMC-A12
Cohort 3 10 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
• IMC-A12
Cohort 4 15 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
• IMC-A12
Cohort 5 21 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
• IMC-A12
Cohort 6 27 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.

Locations

Country	Name	City	State
United States	ImClone Investigational Site	Detroit	Michigan
United States	ImClone Investigational Site	Scottsdale	Arizona
United States	ImClone Investigational Site	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs) or Deaths	Data presented are the number of participants who experienced serious adverse events (SAEs), other non-serious AEs and deaths during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.	Enrollment to study completion up to 215 weeks
Primary	Maximum Tolerated Dose (MTD)	The MTD was defined as the dose preceding the dose level at which 2 participants experienced a dose-limiting toxicity (DLT). A DLT was defined as any Grade 3 or 4 hematologic or nonhematologic toxicity based on Common Terminology Criteria for AE (CTCAE), excluding alopecia, which was considered by the investigator to be definitely, probably, or possibly related to IMC-A12.	6 weeks
Secondary	Maximum Concentration (Cmax) of IMC-A12 Following Multiple Doses		Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Secondary	Observed Serum Concentration of IMC-A12 at 168 Hour Post End of Infusion Following Multiple Doses		Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Secondary	Area Under the Serum Concentration Versus Time Curve of IMC-A12 During One Dosing Interval (AUCt) Following Multiple Doses		Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Secondary	Half-Life (t1/2) of IMC-A12 Following Multiple Doses	Half-Life (t1/2) is the time measured for the plasma concentration of the drug to decrease by one half. The analysis was not performed for the 6 mg/kg and 10 mg/kg dosing groups due to insufficient PK data.	Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Secondary	Clearance Rate of IMC-A12 at Steady State (CLss) Following Multiple Doses	CLss is the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time at steady-state.	Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Secondary	Volume of Distribution of IMC-A12 at Steady State (Vss) Following Multiple Doses	Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug at steady-state. The analysis was not performed for the 6 mg/kg and 10 mg/kg dosing groups due to insufficient PK data.	Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1
Secondary	Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity)	Analysis was not performed due to lack of available assay.	Before the last infusion of each treatment cycle
Secondary	Number of Participants With Best Overall Response	Stable Disease (SD) is neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for progressive disease (PD). PR and PD were assessed by investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PR is =30% decrease in sum of longest diameter of target lesions. PD is =20% increase in sum of longest diameter of target lesions and/or a new lesion. Participants with a global deterioration of their health status requiring discontinuation of treatment without objective evidence of disease progression at that time were to be reported as "symptomatic deterioration"	Enrollment to study completion up to 215 weeks