Clinical trial NCT01288989: A Study of Anti-VEGFR-3 Monoclonal Antibody IMC-3C5 in Subjects With Advanced Solid Tumors
Official title: Phase 1 Study of the Anti-VEGFR-3 Monoclonal Antibody IMC-3C5 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: 2011-02-03
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A dose escalation study to determine the safety and maximum tolerated dose (MTD) of IMC-3C5 in subjects with advanced solid tumors that are refractory to standard therapy or for which no standard therapy is available.

Detailed description: This multicenter study will enroll approximately 40 participants. The actual sample size will vary depending on how many participants are needed to obtain at least 3 complete participants per cohort.

IMC-3C5 will initially be administered once every week (Cohorts 1-4) in a dose escalated manner. The starting dose will be 5 mg/kg weekly (Cohort 1). Dose escalation will proceed to 10 mg/kg (Cohort 2), 20 mg/kg (Cohort 3), and 30 mg/kg (Cohort 4). Based on an analysis of the safety and pharmacokinetic profile of weekly dosing, participants may be enrolled sequentially into 2 every-other-week dose cohorts (Cohorts 5-6, 20 mg/kg and 30 mg/kg). Intermediate doses may also be used.

Eligibility criteria: Inclusion Criteria:

1. Participant has histologic or cytologic confirmation of cancer
2. Participant has an advanced solid tumor that is refractory to standard therapy or for which no standard therapy is available
3. Participant has measurable or nonmeasurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
4. Participant has not received prior chemotherapy or prior treatment with an investigational agent or device within 28 days prior to enrollment(hormone therapy is acceptable)
5. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1, or 2
6. Participant has adequate hematologic, hepatic, renal, and coagulation function
7. Participant has a life expectancy greater than 3 months
8. Participant agrees to use adequate contraception during the study period and for 12 weeks after last dose of investigational agent

Exclusion Criteria:

1. Participant has a known sensitivity to monoclonal antibodies or other therapeutic proteins, or to agents of similar biologic composition as IMC-3C5
2. Participant has received treatment with any monoclonal antibodies including bevacizumab within 6 weeks prior to enrollment
3. Participant has undergone a major surgical procedure, radiation therapy, open biopsy, or has experienced a significant injury within 28 days prior to enrollment
4. Participant has an ongoing or active infection (except as outlined in Exclusion Criterion #11), congestive heart failure, active bleeding or any other serious uncontrolled medical disorder
5. Participant has known or suspected untreated brain or leptomeningeal metastases
6. Participant has uncontrolled hypertension
7. Participant has received an organ transplant
8. Participant has a serious or nonhealing wound, ulcer, or bone fracture
9. Participant has experienced an arterial or venous thromboembolic event within 6 months prior to enrollment
10. Participant currently has peripheral edema requiring diuresis or anasarca
11. Participant has Human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), except subjects who have been on a stable antiviral regimen for at least 12 weeks, have a viral load of \< 50 copies/mL, and a CD4 count of ≥ 200 cells/mm3
12. Participant is currently using or has received a thrombolytic agent within 28 days prior to enrollment
13. Participant is receiving aspirin at a dose higher than 325 mg per day or full-dose anticoagulation
14. Participant if female, is pregnant or is lactating

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline up to 46 months
measure: Number of Participants Reporting Dose-Limiting Toxicity (DLT)
timeFrame: Baseline up to 16 Months
Secondary outcomes:
measure: Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR)
timeFrame: Baseline up to 46 Months
measure: Maximum Concentration (Cmax) of IMC-3C5 - First Infusion
timeFrame: Prior to 1st infusion (Day 1 of Cycle 1), immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168 hours post infusion for cohorts 1-4. Prior to 1st infusion and 1 hour post infusion for cohort 5. (Cycle 1 = 4 - 6 weeks.)
measure: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Drug Concentration (AUC 0-tlast) of IMC-3C5 - First Infusion
timeFrame: Prior to 1st infusion (Day 1 of Cycle 1), immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.)
measure: Maximum Concentration (Cmax) of IMC-3C5 - Fourth Infusion
timeFrame: Prior to 4th infusion (approximately Day 22, Cycle 1), immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. Prior to 4th infusion, 1 hour post infusion for cohort 5. (Cycle 1 = 4-6 weeks.)
measure: Area Under the Concentration-Time Curve During One Dose Interval (AUCtau) of IMC-3C5 (168 Hours) - Fourth Infusion
timeFrame: Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.)
measure: Terminal Half-life (t1/2) of IMC-3C5 - Fourth Infusion
timeFrame: Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.)
measure: Volume of Distribution of IMC-3C5 at Steady State (Vss) - Fourth Infusion
timeFrame: Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.)
measure: Clearance (Cl) of IMC-3C5 at Steady State - Fourth Infusion
timeFrame: Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.)
measure: Minimum Concentration (Cmin) of IMC-3C5 - Fourth Infusion
timeFrame: Prior to 4th infusion (approximately Day 22) of Cycle 1 for cohorts 1-5. (Cycle 1 = 4 - 6 weeks.)
measure: Anti-IMC-3C5 Antibody Assessment
timeFrame: Predose: First and fourth infusions (Cycle 1), ninth infusion (Cycle 3), 15th infusion (Cycle 4), 21st infusion (Cycle 6), 27th infusion (Cycle 7). (Cycle 1 = 4 - 6 weeks. Subsequent cycles = 4 weeks.)
Other outcomes:
Locations:
city: Peoria
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: Illinois
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: Boston
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: Massachusetts
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:
citation: Saif MW, Knost JA, Chiorean EG, Kambhampati SR, Yu D, Pytowski B, Qin A, Kauh JS, O'Neil BH. Phase 1 study of the anti-vascular endothelial growth factor receptor 3 monoclonal antibody LY3022856/IMC-3C5 in patients with advanced and refractory solid tumors and advanced colorectal cancer. Cancer Chemother Pharmacol. 2016 Oct;78(4):815-24. doi: 10.1007/s00280-016-3134-3. Epub 2016 Aug 26.