A Study of IMC-RON8 in Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01119456
First received: May 6, 2010
Last updated: January 8, 2014
Last verified: January 2014
  Purpose

A dose escalation study to determine the maximum tolerated dose of IMC-RON8 in patients with solid tumor. Patients can either be dosed once a week, or once every other week.


Condition Intervention Phase
Cancer
Biological: IMC-RON8
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Study of the Anti-Ron Receptor Monoclonal Antibody IMC-RON8 in Patients With Advanced Solid Tumors Who No Longer Respond to Standard Therapy or for Whom No Standard Therapy is Available

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • To establish the safety profile and maximum tolerated dose (MTD) of IMC-RON8 [ Time Frame: 36 Months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics (PK), maximum concentration (Cmax) of IMC-RON8 [ Time Frame: 36 Months ] [ Designated as safety issue: No ]
  • Pharmacokinetics, area under the curve (AUC) of IMC-RON8 [ Time Frame: 36 Months ] [ Designated as safety issue: No ]
  • Immunogenicity of IMC-RON8 [ Time Frame: 36 Months ] [ Designated as safety issue: Yes ]
    A sample will be considered positive for anti-IMC-RON8 antibodies if it exhibits a post-baseline antibody level exceeding the baseline anti-IMC-RON8 antibody level

  • Pharmacodynamics of IMC-RON-8 [ Time Frame: 36 Months ] [ Designated as safety issue: No ]
    Determine the circulating levels of macrophage-stimulating protein on selected DNA, RNA, protein, and serum targets.

  • Antitumor activity of IMC-RON8 in the treatment of solid tumors [ Time Frame: 36 Months ] [ Designated as safety issue: No ]

Estimated Enrollment: 52
Study Start Date: May 2010
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMC-RON8 Biological: IMC-RON8

5 mg/kg intravenously (i.v.)

Once a week for each 4-week treatment cycle, for a total of four doses per cycle.

Cohort 1

Other Name: Narnatumab
Biological: IMC-RON8

10 mg/kg intravenously (i.v.)

Once a week for each 4-week treatment cycle, for a total of four doses per cycle.

Cohort 2

Other Name: Narnatumab
Biological: IMC-RON8

15 mg/kg intravenously (i.v.)

Once a week for each 4-week treatment cycle, for a total of four doses per cycle.

Cohort 3

Other Name: Narnatumab
Biological: IMC-RON8

15 mg/kg intravenously (i.v.)

Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.

Cohort 4

Other Name: Narnatumab
Biological: IMC-RON8

20 mg/kg intravenously (i.v.)

Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.

Cohort 5

Other Name: Narnatumab
Biological: IMC-RON8

25 or 30 mg/kg intravenously (i.v.)

Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.

Cohort 6

Other Name: Narnatumab
Biological: IMC-RON8

30, 35, or 40 mg/kg intravenously (i.v.)

Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.

Cohort 7

Other Name: Narnatumab
Biological: IMC-RON8

20 or 25 mg/kg intravenously (i.v)

Once every week for each 4-week treatment cycle, for a total of four doses per cycle.

Cohort 8

Other Name: Narnatumab

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient has histologically-confirmed advanced primary or recurrent solid tumors that have not responded to standard therapy or for which no standard therapy is available
  • The patient has measurable or non-measurable disease
  • The patient has not received major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy within 28 days prior to the first dose of study therapy
  • The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-2
  • The patient has adequate hematologic function
  • The patient has adequate renal function as defined by serum creatinine ≤ 1.5 x the institutional ULN
  • The patient has a life expectancy > 3 months

Exclusion Criteria:

  • The patient has received chemotherapy or therapeutic radiation therapy within 28 days prior to the first dose of study therapy
  • The patient has ongoing toxicities of > Grade 1 associated with any prior treatment
  • The patient has a known sensitivity to monoclonal antibodies or other therapeutic agents, or to agents of similar biologic composition as IMC-RON8
  • The patient has received treatment with any monoclonal antibodies within 6 weeks prior to first dose of study therapy
  • The patient has received treatment with agents specifically targeting the Ron ligand or receptor within 6 weeks prior to first dose of study therapy
  • The patient has undergone a major surgical procedure, open biopsy, or experienced a significant traumatic injury within 28 days prior to the first dose of study therapy
  • The patient has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia (well controlled atrial fibrillation is permitted), psychiatric illness/social situations, active bleeding, or any other serious uncontrolled medical disorders in the opinion of the investigator
  • The patient has known or suspected brain or leptomeningeal metastases (patients with a history of brain metastases must have received definitive surgery or radiotherapy, be clinically stable, and may not be taking steroids; patients receiving anticonvulsants are eligible)
  • The patient has a serious or nonhealing active wound, ulcer, or bone fracture
  • The patient is currently using or has received a thrombolytic agent within 28 days prior to first dose of study therapy
  • The patient is receiving full-dose warfarin (patients receiving low-dose warfarin to maintain the patency of permanent, indwelling intravenous catheters are eligible if the international normalized ratio is < 1.5)
  • The patient is receiving intravenous heparin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01119456

Locations
United States, Indiana
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
Indianapolis, Indiana, United States, 46202
United States, Michigan
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
Detroit, Michigan, United States, 48201
United States, New York
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
New York, New York, United States, 10065
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01119456     History of Changes
Other Study ID Numbers: 13958, CP21-0901, I5D-IE-JRCA
Study First Received: May 6, 2010
Last Updated: January 8, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Eli Lilly and Company:
Tumors
Macrophage stimulating 1 receptor, human
RON protein
RON receptor protein tyrosine kinase

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014