Study of IMC-1121B in Patients With Tumors That Have Not Responded to Therapy

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 37

Inclusion Criteria

Histopathologically-documented, measurable or evaluable (non-measurable), advanced primary or recurrent solid tumors who have not responded to standard therapy or for whom no standard therapy is available.
ECOG performance status score of ≤ 2 at study entry
Able to provide written informed consent
A life expectancy of > 3 months
Adequate hematologic function, as defined by: ANC ≥ 1500/mm^3, hemoglobin level ≥ 10 gm/dL, platelet count ≥ 100,000/mm^3
Adequate hepatic function, as defined by: total bilirubin level ≤ 1.5 x the ULN, AST and 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
Use of effective contraception (per the institutional standard), if procreative potential exists
Adequate recovery from recent surgery, chemotherapy, and radiation therapy. At least 28 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy (palliative radiation therapy is allowed).
Accessible for treatment and follow-up. Patients enrolled in this trial must be treated at the participating center.

Exclusion Criteria

Patients with large centrally-located pulmonary lesions adjacent to or invading large blood vessels.
Patients who have had chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or patients with ongoing side effects ≥ grade 2 due to agents administered more than 28 days earlier.
Prior left chest wall radiotherapy or a cumulative anthracycline dose ≥ 300mg/m2 (if the ejection fraction is within normal institutional limits, the patient can be enrolled).
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 ≥ 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, uncontrolled diabetes, psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements, patients with symptomatic brain metastases
A serious or nonhealing active wound, ulcer, or bone fracture
Known HIV positivity
A major surgical procedure, an open biopsy, or a significant injury within 28 days prior to treatment
Current or recent use (within 28 days) of a thrombolytic agent
Current or recent use (within 28 days) of full-dose warfarin
Chronic daily treatment with aspirin (>325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function
History or clinical evidence of a deep venous or arterial thrombosis (including pulmonary embolism) within 6 months prior to study entry
Proteinuria ≥1+ by routine urinalysis (patients with a protein value of ≤ 500mg confirmed by a 24-hour urine collection are eligible)
Pregnant (confirmed by serum beta human chorionic gonadotropin [βHCG]) or breast feeding
Prior treatment with bevacizumab or other agents specifically targeting VEGF ligand or receptor within 6 weeks of study entry
Monoclonal antibodies within 6 weeks of study entry
Positive anti-IMC-1121B 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 the employees.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IMC-1121B	IMC-1121B	All patients will receive intravenous infusions of IMC-1121B with the dose depending on which cohort they are enrolled into. A minimum of three patients will be enrolled in each cohort. A completed patient will be either a patient who completes the 4-week treatment cycle and 2-week observation period (for a total of 6 weeks), or a patient who discontinues therapy for an IMC-1121B-related toxicity. Toxicity data for each cohort will be reviewed prior to dose escalation. When all patients complete a cohort, dose escalation to the next cohort will occur.
IMC-1121B	1121B	All patients will receive intravenous infusions of IMC-1121B with the dose depending on which cohort they are enrolled into. A minimum of three patients will be enrolled in each cohort. A completed patient will be either a patient who completes the 4-week treatment cycle and 2-week observation period (for a total of 6 weeks), or a patient who discontinues therapy for an IMC-1121B-related toxicity. Toxicity data for each cohort will be reviewed prior to dose escalation. When all patients complete a cohort, dose escalation to the next cohort will occur.

Primary Outcome Measures

Name	Time	Method
Number of participants with Adverse Events (AEs)	6 weeks
Maximum Tolerated Dose	6 weeks

Secondary Outcome Measures

Name	Time	Method
Maximum concentration (Cmax), cohorts 1, 2, 3, 4, 5, 6. and 7	6 weeks
Minimum concentration (Cmin), cohorts 1, 2, 3, 4, 5, 6. and 7	6 weeks
Area under concentration (AUC), cohorts 1, 2, 3, 4, 5, 6. and 7	6 weeks
Half-life (t 1/2), cohorts 1, 2, 3, 4, 5, 6. and 7	6 weeks
Clearance (Cl) rate drug is completely removed, cohorts 1, 2, 3, 4, 5, 6. and 7	6 weeks
Volume of distribution (Vss) at steady state, cohorts 1, 2, 3, 4, 5, 6. and 7	6 weeks
Serum Anti-IMC-1121B Antibody Assessment (immunogenicity)	6 weeks
Change in tumor size from Baseline Measurement	6 weeks

Study of IMC-1121B in Patients With Tumors That Have Not Responded to Therapy

Recruitment & Eligibility

Study & Design

Trial Locations

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