Clinical trial NCT01346358: A Study of IMC-CS4 in Subjects With Advanced Solid Tumors
Official title: Phase 1 Study of IMC-CS4, a Monoclonal Antibody Targeted to the CSF-1 Receptor (CSF-1R), In Subjects With Advanced Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy is Available
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Advanced Solid Tumors
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-05-03
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: A dose escalation study to establish the safety profile and characterize the pharmacokinetic profile of IMC-CS4 in the treatment of subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy is available.


Eligibility criteria: Inclusion Criteria:

* Subject has histologic or cytologic confirmation of advanced solid tumors that is refractory to standard therapy or for which no standard therapy is available
* Subject has measurable or nonmeasurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
* Subject has resolution to grade ≤1 by NCI-CTCAE (Common Toxicity Criteria for Adverse Effects) Version 4.03 of all clinically significant toxic effects of prior treatment
* Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Subject has adequate hematologic, hepatic, renal, and coagulation function
* Subject has a life expectancy greater than 3 months
* Subject agrees to use adequate contraception during the study period and for 12 weeks after last dose of study therapy
* Subject must undergo mandatory biopsies, including one pretreatment and one post treatment tumor biopsy procedure

Exclusion Criteria:

* Subject has experienced acute pathologic fracture or spinal cord compression within 28 days prior to first dose of study therapy
* Subject has a known hypersensitivity to monoclonal antibodies or to agents of similar biologic composition as IMC-CS4.
* Subject has received treatment with any monoclonal antibodies within 4 weeks prior to first dose of study therapy
* Subject has undergone a major surgical procedure, open biopsy, radiofrequency ablation or has experienced a significant injury within 28 days prior to enrollment
* Subject has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer or in situ neoplasm
* Subject has an ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, active bleeding or any other serious uncontrolled medical disorder
* Subject has known or suspected primary brain or leptomeningeal metastases
* Subject has leukemia or lymphoma
* Subject is know to have active tuberculosis, leishmaniasis, or listeriosis
* Subjects with known history, or clinical or laboratory evidence of liver disease
* Subject has a known active hepatitis B or C infection, Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
* Subject if female, is pregnant or breastfeeding
* Subject has received an organ transplant

Primary outcomes:
measure: Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4
timeFrame: Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1
measure: Pharmacokinetics - Minimum Concentration (Cmin) of IMC-CS4
timeFrame: Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1
measure: Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4
timeFrame: Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1
measure: Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4
timeFrame: Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1
measure: Pharmacokinetics -Clearance (Cl) of IMC-CS4
timeFrame: Predose, 1, 2, 4 and 8 hours post dose of Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22 and Cycle 3 Day 1
Secondary outcomes:
measure: Recommend Phase 2 Dose (RP2D) of IMC-CS4
timeFrame: Cycle 1 (6 Days)
measure: Percentage of Participants With Anti-IMC-CS4 Antibody Assessment
timeFrame: Up To 6 Months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic & Research Institute
state: California
city: San Francisco
country: United States
facility: Univ of California San Francisco
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: New York
country: United States
facility: Columbia University College of Phys & Surgeons
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
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:
citation: Dowlati A, Harvey RD, Carvajal RD, Hamid O, Klempner SJ, Kauh JSW, Peterson DA, Yu D, Chapman SC, Szpurka AM, Carlsen M, Quinlan T, Wesolowski R. LY3022855, an anti-colony stimulating factor-1 receptor (CSF-1R) monoclonal antibody, in patients with advanced solid tumors refractory to standard therapy: phase 1 dose-escalation trial. Invest New Drugs. 2021 Aug;39(4):1057-1071. doi: 10.1007/s10637-021-01084-8. Epub 2021 Feb 23.