A Study of IMC-CS4 in Subjects With Advanced Solid Tumors

Phase 1

Completed

• Conditions: Neoplasms
• Interventions: Biological: IMC-CS4

• Registration Number: NCT01346358
• Lead Sponsor: Eli Lilly and Company

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-04-29
• Study First Submitted QC: 2011-04-29
• Study First Posted: 2011-05-03
• Study Start: 2011-06
• Primary Completion: 2018-05-31
• Study Completion: 2018-05-31
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-20
• Last Update Posted: 2018-07-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 72

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IMC-CS4 Weight Based Dosing	IMC-CS4	Participants received 2.5 mg/kg once weekly (QW), 0.3 mg/kg QW, 0.6 mg/kg QW, 1.25 mg/kg every two weeks (Q2W) and1.25 mg/kg QW of IMC CS4 by intravenous infusion in Part A.
IMC-CS4 Non-Weight Based Dosing	IMC-CS4	Participants received 100 mg QW, 100 mg QW on weeks 1, 2, 4 and 5 and 150 mg QW of IMC CS4 by intravenous infusion in Part B.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK) - Maximum Concentration (Cmax) of IMC-CS4	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	Pharmacokinetics (PK) - Maximum concentration (Cmax) of IMC-CS4.
Pharmacokinetics - Minimum Concentration (Cmin) of IMC-CS4	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	Pharmacokinetics - Minimum concentration (Cmin) of IMC-CS4.
Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4	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	Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4.
Pharmacokinetics - Volume of Distribution at Steady State (Vss) of IMC-CS4	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	Pharmacokinetics - Volume of distribution at steady state (Vss) of IMC-CS4.
Pharmacokinetics -Clearance (Cl) of IMC-CS4	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	Pharmacokinetics -Clearance (Cl) of IMC-CS4.

Secondary Outcome Measures

Name	Time	Method
Recommend Phase 2 Dose (RP2D) of IMC-CS4	Cycle 1 (6 Days)	The recommended Phase 2 dose was the highest dose where less than 1/3 of participants experienced dose limiting toxicities (DLTs). A DLT is defined as an adverse event (AE) occurring during Cycle 1 that fulfilled 1 of the following criteria: Any Common Terminology Criteria for Adverse Events (CTCAE), version (v) 4.0 Grade 4 neutropenia lasting ≥ 7 days, Grade 3 or 4 neutropenia complicated by fever ≥38.0°C or infection, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia complicated by hemorrhage, Grade 3 or 4 anemia, Grade ≥3 AST/ALT elevation, Grade ≥2 AST/ALT elevation and Grade ≥2 bilirubin elevation and Grade 3 or 4 nonhematologic toxicity. A summary of other nonserious AEs and all Serious Adverse Events (SAE), regardless of causality is located in the Reported Adverse Event section.
Percentage of Participants With Anti-IMC-CS4 Antibody Assessment	Up To 6 Months	The overall percentage of participants with treatment-emergent positive for anti-IMC-CS4 antibodies during the study. Participants were considered positive for anti-IMC-CS4 antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the normal anti-IMC-CS4 level seen in healthy untreated individuals.

Trial Locations

Locations (6)

Emory University; 🇺🇸 Atlanta, Georgia, United States

Ohio State University Medical Center; 🇺🇸 Columbus, Ohio, United States

University Hospitals Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

Columbia University College of Phys & Surgeons; 🇺🇸 New York, New York, United States

The Angeles Clinic & Research Institute; 🇺🇸 Los Angeles, California, United States

Univ of California San Francisco; 🇺🇸 San Francisco, California, United States