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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00785941
• Other study ID #: 13933
• Secondary ID: CP13-0502I5A-IE-
• Status: Completed
• Phase: Phase 1
• First received: November 4, 2008
• Last updated: October 12, 2011
• Start date: April 2006
• Est. completion date: November 2007

Study information

• Verified date: October 2011
• Source: ImClone LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: November 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Biological:
• IMC-A12
Cohort 1 6 mg/kg I.V., once every other week for 4 weeks
• IMC-A12
Cohort 2 10 mg/kg I.V., once every other week for 4 weeks
• IMC-A12
Cohort 3 15 mg/kg I.V., once every other week for 4 weeks
• IMC-A12
Cohort 4 21 mg/kg I.V., once every other week for 4 weeks
• IMC-A12
Cohort 5 27 mg/kg I.V., once every other week for 4 weeks

Locations

Country	Name	City	State
United States	ImClone Investigational Site	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
ImClone LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events (AEs)		8 weeks	Yes
Primary	Maximum Tolerated Dose		8 weeks	No
Secondary	Maximum concentration (Cmax), cohorts 1, 2, 3, 4, and 5		8 weeks	No
Secondary	Minimum concentration (Cmin), cohorts 1, 2, 3, 4, and 5		8 weeks	No
Secondary	Area under concentration (AUC), cohorts 1, 2, 3, 4, and 5		8 weeks	No
Secondary	Half-life (t 1/2), cohorts 1, 2, 3, 4, and 5		8 weeks	No
Secondary	Clearance (Cl) rate drug is completely removed, cohorts 1, 2, 3, 4, and 5		8 weeks	No
Secondary	Volume of distribution (Vss) at steady state, cohorts 1, 2, 3, 4, and 5		8 weeks	No
Secondary	Serum Anti-IMC-A12 Antibody Assessment (immunogenicity)		8 weeks	No
Secondary	Change in tumor size from Baseline Measurement		8 weeks	No