Clinical trial NCT01119456: A Study of IMC-RON8 in Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: Tumors
Macrophage stimulating 1 receptor, human
RON protein
RON receptor protein tyrosine kinase
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-05-07
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: A dose escalation study to determine the maximum tolerated dose of IMC-RON8 in participants with solid tumors. Participants can either be dosed once a week, or once every other week.


Eligibility criteria: Inclusion Criteria:

* The participant 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 participant has measurable or non-measurable disease
* The participant 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 participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-2
* The participant has adequate hematologic function
* The participant has adequate renal function as defined by serum creatinine ≤1.5 times the institutional upper limit of normal (ULN)
* The participant has a life expectancy \>3 months

Exclusion Criteria:

* The participant has received chemotherapy or therapeutic radiation therapy within 28 days prior to the first dose of study therapy
* The participant has ongoing toxicities of \>Grade 1 associated with any prior treatment
* The participant has a known sensitivity to monoclonal antibodies or other therapeutic agents, or to agents of similar biologic composition as IMC-RON8
* The participant has received treatment with any monoclonal antibodies within 6 weeks prior to first dose of study therapy
* The participant has received treatment with agents specifically targeting the RON ligand or receptor within 6 weeks prior to first dose of study therapy
* The participant 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 participant 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 participant has known or suspected brain or leptomeningeal metastases (participants with a history of brain metastases must have received definitive surgery or radiotherapy, be clinically stable, and may not be taking steroids; participants receiving anticonvulsants are eligible)
* The participant has a serious or nonhealing active wound, ulcer, or bone fracture
* The participant is currently using or has received a thrombolytic agent within 28 days prior to first dose of study therapy
* The participant is receiving full-dose warfarin (participants receiving low-dose warfarin to maintain the patency of permanent, indwelling intravenous catheters are eligible if the international normalized ratio is \<1.5)
* The participant is receiving intravenous heparin

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of IMC-RON8
timeFrame: Baseline through end of study treatment (up to 48 weeks)
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8
timeFrame: First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
measure: PK: Area Under the Curve (AUC) of IMC-RON8
timeFrame: First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
measure: Immunogenicity of IMC-RON8
timeFrame: Prior to first infusion through study completion (up to 52 weeks)
measure: Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8)
timeFrame: Prior to first infusion through 1 hour post last infusion (end of study treatment, up to 48 weeks)
measure: Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors)
timeFrame: Baseline to measured PD (up to 48 weeks)
Other outcomes:
measure: Number of Participants Who Died
timeFrame: Baseline through study completion (up to 52 weeks)
Locations:
city: Indianapolis
country: United States
facility: 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
state: Indiana
city: Detroit
country: United States
facility: 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
state: Michigan
city: New York
country: United States
facility: 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
state: New York
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: