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Trial record 45 of 93977 for:    5

A Study of Anti-VEGFR-3 Monoclonal Antibody IMC-3C5 in Subjects With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT01288989
Recruitment Status : Completed
First Posted : February 3, 2011
Results First Posted : June 17, 2019
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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.

Condition or disease Intervention/treatment Phase
Neoplasms Biological: IMC-3C5 Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : March 2011
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Arm Intervention/treatment
Experimental: IMC-3C5
Participants receiving IMC-3C5 intravenously
Biological: IMC-3C5
Escalating doses of IMC-3C5 administered intravenously (i.v.), weekly or every other week
Other Name: LY3022856




Primary Outcome Measures :
  1. Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to 46 months ]
    AEs include serious AEs (SAEs). AEs do not distinguish whether the events are treatment-emergent. A summary of serious and other non-serious AEs, regardless of causality, is presented in the Reported Adverse Event module.

  2. Number of Participants Reporting Dose-Limiting Toxicity (DLT) [ Time Frame: Baseline up to 16 Months ]

    A DLT was defined as any adverse event (National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0) considered by the investigator to be definitely, probably, or possibly related to IMC-3C5, that occurred during the DLT Assessment Period (weeks 1 through 6) as follows:

    • Any Grade 3 or 4 hematologic toxicity
    • Any Grade 3 or 4 nonhematologic toxicity (excluding fatigue or anorexia lasting <7 days, or Grade 3 nausea and/or vomiting that persisted for <2 days following appropriate supportive care intervention)


Secondary Outcome Measures :
  1. Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR) [ Time Frame: Baseline up to 46 Months ]
    Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Progressive Disease (PD) was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir. Stable Disease (SD) was defined as small changes that did not meet above criteria.

  2. Maximum Concentration (Cmax) of IMC-3C5 - First Infusion [ Time Frame: 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.) ]
  3. Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Drug Concentration (AUC 0-tlast) of IMC-3C5 - First Infusion [ Time Frame: 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.) ]
  4. Maximum Concentration (Cmax) of IMC-3C5 - Fourth Infusion [ Time Frame: 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.) ]
  5. Area Under the Concentration-Time Curve During One Dose Interval (AUCtau) of IMC-3C5 (168 Hours) - Fourth Infusion [ Time Frame: 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.) ]
  6. Terminal Half-life (t1/2) of IMC-3C5 - Fourth Infusion [ Time Frame: 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.) ]
  7. Volume of Distribution of IMC-3C5 at Steady State (Vss) - Fourth Infusion [ Time Frame: 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.) ]
  8. Clearance (Cl) of IMC-3C5 at Steady State - Fourth Infusion [ Time Frame: 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.) ]
  9. Minimum Concentration (Cmin) of IMC-3C5 - Fourth Infusion [ Time Frame: Prior to 4th infusion (approximately Day 22) of Cycle 1 for cohorts 1-5. (Cycle 1 = 4 - 6 weeks.) ]
    Trough concentration (Ctrough) prior to fourth infusion of Cycle 1.

  10. Anti-IMC-3C5 Antibody Assessment [ Time Frame: 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.) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01288989


Locations
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United States, Illinois
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.
Peoria, Illinois, United States, 61615
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, Massachusetts
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.
Boston, Massachusetts, United States, 02111
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, 10029
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01288989     History of Changes
Other Study ID Numbers: 14247
CP23-1001 ( Other Identifier: ImClone Systems )
I5G-IE-JBCA ( Other Identifier: Eli Lilly and Company )
First Posted: February 3, 2011    Key Record Dates
Results First Posted: June 17, 2019
Last Update Posted: June 17, 2019
Last Verified: March 2019
Keywords provided by Eli Lilly and Company:
Advanced Solid Tumors
Additional relevant MeSH terms:
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Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs