Safety Study of IMC-18F1,to Treat Advanced Solid Tumors in Subjects That no Longer Respond to Standard Therapy

NCT00782002 | Completed Phase 1 DMC

• 3 other identifiers: 13941CP14-0501I4Y-IE-JCDA
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine if IMC-18F1 is safe for patients, and also to determine the best dose of IMC-18F1 to give to patients.

Conditions

Advanced Solid Tumors

Keywords

Solid Tumors; VEGF-A; stromal cells; endothelial cells; malignant cells

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  6 weeks

Secondary Outcomes (3)

• Pharmacokinetics

  6 weeks

• Antitumor Activity of IMC-18F1 Monotherapy

  6 Weeks

• Pharmacodynamics

  6 Weeks

Study Arms (1)

IMC-18F1

EXPERIMENTAL

Biological: IMC-18F1

Interventions

IMC-18F1 BIOLOGICAL

Cohorts 1-4 will receive IMC-18F1 intravenously for 4 weekly infusions, followed by a 2-week observation period. Cohort 5 will receive IMC-18F1 intravenously every other week for the first 6 weeks of therapy. Cohort 6 will receive IMC-18F1 every 3 weeks for the first 6 weeks for therapy. The starting dose in Cohort 1 will be 2mg/kg. The maximum dose of IMC-18F1 will not exceed 16mg/kg administered every week, 15mg/kg administered every other week, and 20mg/kg administered every 3 weeks. Dose escalation of 100% (2 x previous dose) if no dose limiting toxicities (DLTs) are observed in the first three patients within a cohort during the initial 6-week therapy period. Dose escalation increment will be reduced to 50% (1.5 x previous dose) following the occurrence of either grade 2 or higher AEs in 2 or more patients that are possibly, probably, or definitely-related to study medication or one DLT during the initial 6-week therapy period. No intrapatient dose escalation is allowed.

IMC-18F1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histopathologically-documented, measurable or non measurable {evaluable}, advanced solid tumors refractory to standard therapy or for which no standard therapy is available (see Section 10.2, Tumor Response, for the definition of measurable and non measurable {evaluable} disease).
• Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2 at study entry.
• Able to provide written informed consent.
• Age 18 years or older.
• A life expectancy of \>3 months.
• Adequate hematologic function, as defined by:
• an absolute neutrophil count ≥1500/mm3
• a hemoglobin level ≥ 9gm/dL
• a platelet count ≥100,000/mm3
• Adequate hepatic function, as defined by:
• a total bilirubin level ≤1.5 x the 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.
• 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).

You may not qualify if:

• Patients who have had chemotherapy or therapeutic radiotherapy within 28 days prior to entering the study or patients with ongoing side effects ≥ grade 2 due to agents administered more than 28 days earlier.
• 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)
• left ventricular ejection fraction (LVEF) of \<50%. If a baseline MUGA shows a \<50% ejection fraction, then a confirmatory ultrasound should be performed. If it is \<50%, the patient is excluded from the study
• unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
• uncontrolled hypertension (systolic blood pressure \>150 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 \[Common Terminology Criteria for Adverse Events {CTCAE}, Version 3.0, grade 3\] or asymptomatic sustained ventricular tachycardia)
• uncontrolled diabetes
• psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements
• Patients with progressive or symptomatic brain or leptomeningeal metastases. (Patients with a history of brain metastases must have received definitive surgery or radiotherapy, be clinically stable, and not taking steroids; anti-seizure medications are allowed).
• A serious or nonhealing active wound, ulcer, or bone fracture.
• Known human immunodeficiency virus positivity.
• A major surgical procedure, an open biopsy, or a significant traumatic injury within 28 days prior to treatment.
• Current or recent use (within 28 days) of a thrombolytic agent.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (2)

ImClone Investigational Site

Detroit, Michigan, 48201, United States

Location

ImClone Investigational Site

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

• LoRusso PM, Krishnamurthi S, Youssoufian H, Hall N, Fox F, Dontabhaktuni A, Grebennik D, Remick S. Icrucumab, a fully human monoclonal antibody against the vascular endothelial growth factor receptor-1, in the treatment of patients with advanced solid malignancies: a Phase 1 study. Invest New Drugs. 2014 Apr;32(2):303-11. doi: 10.1007/s10637-013-9998-8. Epub 2013 Aug 1.

  PMID: 23903897 DERIVED

MeSH Terms

Interventions

IMC-18F1

Study Officials

• E-mail: ClinicalTrials@ ImClone.com

  Eli Lilly and Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 27, 2008
• First Posted: October 29, 2008
• Study Start: July 1, 2006
• Primary Completion: March 1, 2009
• Study Completion: November 1, 2009
• Last Updated: September 30, 2010

Record last verified: 2010-09

Locations

US (2)