Study of IMC-1121B in Patients With Advanced Solid Tumors Not Responding To Standard Therapy

NCT00786383 | Completed Phase 1

• 3 other identifiers: 13919CP12-0402I4T-IE-JVBN
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

Brief Summary

We are conducting a research study for tumors that have not responded to prior treatment. The subject will receive an investigational drug called IMC-1121B. ImClone LLC, the maker of IMC-1121B, is running this research study. We believe that IMC-1121B blocks the growth factors made by the cancer cells, so new blood vessels do not grow. It is believed that without the new blood vessels, the cancer or tumor will not get the oxygen and food that it needs to grow. This may stop the cancer from growing or spreading and the tumor cells may die. Since normal blood vessels have already formed in adults, it might be possible to stop tumor growth without harming normal cells.

Conditions

Cancer

Keywords

Phase I; cancer; solid tumors; 1121B; VEGFR-2; Anti-Vascular Endothelial Growth Factor Receptor 2

Outcome Measures

Primary Outcomes (2)

• Number of participants with Adverse Events (AEs)

  8 Weeks

• Maximum Tolerated Dose

  8 Weeks

Secondary Outcomes (8)

• Maximum concentration (Cmax), cohorts 1, 2, 3, 4, and 5

  8 Weeks

• Minimum concentration (Cmin), cohorts 1, 2, 3, 4, and 5

  8 Weeks

• Area under concentration (AUC), cohorts 1, 2, 3, 4, and 5

  8 Weeks

• Half-life (t 1/2), cohorts 1, 2, 3, 4, and 5

  8 Weeks

• Clearance (Cl) rate drug is completely removed, cohorts 1, 2, 3, 4, and 5

  8 Weeks

Study Arms (1)

IMC-1121B

EXPERIMENTAL

IMC-1121B injectable solution at a concentration of 5 mg/mL in single-use vials containing 100 mg/20 mL or 250 mg/50 mL of product, administered intravenously at an initial dose of 6 mg/kg.A minimum of three patients will be enrolled into each cohort. When all patients complete a cohort, dose escalation to the next cohort will occur.

Biological: IMC-1121B; Biological: 1121B

Interventions

IMC-1121B BIOLOGICAL

Cohort 1 6 mg/kg I.V., once every other week for 4 weeks

IMC-1121B

1121B BIOLOGICAL

Cohort 2 8mg/kg I.V., once every other week for 4 weeks

IMC-1121B

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 evaluable (non-measurable), advanced primary or recurrent solid tumors who have not responded to standard therapy or for whom no standard therapy is available
• Eastern Cooperative Oncology Group (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:
• an absolute neutrophil count ≥1500/mm3
• a hemoglobin level ≥10 gm/dL
• a platelet count ≥100,000/mm3
• Adequate hepatic function, as defined by:
• a 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.
• Use of effective contraception , 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
• Accessible for treatment and follow-up. Patients enrolled in this trial must be treated at the participating center.

You may not qualify if:

• 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 ≥300 mg/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 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 or asymptomatic sustained ventricular tachycardia)
• uncontrolled diabetes
• 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 have received definitive surgery or radiotherapy, be clinically stable, and not taking steroids; anticonvulsants are allowed)
• A serious or nonhealing active wound, ulcer, or bone fracture.
• Known human immunodeficiency-positivity.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (3)

ImClone Investigational Site

Indianapolis, Indiana, 46202-5112, United States

Location

ImClone Investigational Site

Durham, North Carolina, 27710, United States

Location

ImClone Investigational Site

Philadelphia, Pennsylvania, 19111, United States

Location

Related Publications (1)

• Chiorean EG, Hurwitz HI, Cohen RB, Schwartz JD, Dalal RP, Fox FE, Gao L, Sweeney CJ. Phase I study of every 2- or 3-week dosing of ramucirumab, a human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2 in patients with advanced solid tumors. Ann Oncol. 2015 Jun;26(6):1230-1237. doi: 10.1093/annonc/mdv144. Epub 2015 Mar 18.

  PMID: 25787923 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Ramucirumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: November 4, 2008
• First Posted: November 6, 2008
• Study Start: February 1, 2006
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: August 19, 2013

Record last verified: 2013-08

Locations

US (3)