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Study of IMC-11F8 in Participants With Advanced Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01088464
First received: March 16, 2010
Last updated: December 9, 2016
Last verified: December 2016
  Purpose
This study is to establish the safety and pharmacokinetic (PK) profile of IMC-11F8, administered either: (1) in a 3-week cycle; or (2) in a 2-week cycle to Japanese participants with advanced solid tumors who have not responded to standard therapy or for whom no standard therapy is available.

Condition Intervention Phase
Neoplasms Biological: IMC-11F8 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of IMC-11F8 in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Number of Participants With 1 or More Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 24 weeks plus 30 days post last dose of study drug ]
    Data presented are the number of participants who experienced 1 or more TEAEs or SAEs regardless of causality. An adverse event was considered as TEAE if it occurred any time after the administration of the first dose of study drug or up to 30 days after the last dose of study treatment or if it occurred prior to the first dose and worsened while on treatment. A summary of SAEs and other non-SAEs regardless of causality is located in the Reported Adverse Events module.

  • Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Necitumumab After a Single Dose [ Time Frame: Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 hours (h) after end of infusion. Cohort 2: predose, immediately after infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion ]
  • PK: Cmax of Necitumumab After Multiple Doses [ Time Frame: Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion ]
    Cmax at steady state (after the last dose of the initial 6-week treatment cycle).

  • PK: Minimum Concentration (Cmin) of Necitumumab After a Single Dose [ Time Frame: Cycle 1; Cohorts 1, 2 and 3: prior to second infusion ]
    Cmin is defined as the minimum concentration the drug achieved after administration of first infusion and prior to the administration of second infusion.

  • PK: Cmin of Necitumumab After Multiple Doses [ Time Frame: Cycle 1; Cohorts 1and 3: prior to fourth infusion. Cohort 2: prior to third infusion ]
    Cmin was calculated prior to the last dose of the initial 6-week treatment cycle.

  • PK: Area Under the Concentration-Time Curve From Time 0 to Last Time Point [AUC (0-tlast)] of Necitumumab After a Single Dose [ Time Frame: Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion ]
  • PK: Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)] of Necitumumab After a Single Dose [ Time Frame: Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion ]
    AUC(0-∞) was calculated only for participants in Cohort 2 as the percentage of AUC extrapolated beyond tlast was greater than 30% for all the remaining participants.

  • PK: Area Under the Concentration-Time Curve From Time 0 to 336 h Postdose [AUC(0-336)] of Necitumumab After Multiple Doses [ Time Frame: Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion ]
    Steady state AUC(0-336) values are reported.

  • PK: Half-Life (t½) of Necitumumab After a Single Dose [ Time Frame: Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion ]
    The t½ is defined as the time taken for study drug in blood to decrease to half of its concentration.

  • PK: t½ of Necitumumab After Multiple Doses [ Time Frame: Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion ]
    The t½ is defined as the time taken for study drug in blood to decrease to half of its concentration.

  • PK: Clearance (CL) of Necitumumab After a Single Dose [ Time Frame: Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion ]
    CL is defined as the volume of plasma that is cleared of study drug per unit time. CL was not analyzed for participants in Cohorts 1 and 3 as CL is derived from AUC(0-∞). AUC(0-∞) was calculated only for participants in Cohort 2 as the percentage of AUC extrapolated beyond tlast was greater than 30% for the remaining participants.

  • PK: CL of Necitumumab After Multiple Doses [ Time Frame: Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion ]
    CL is defined as the volume of plasma that is cleared of study drug per unit time. Data did not allow calculation of CL for participants in Cohorts 1 and 3.

  • PK: Steady-State Volume of Distribution (Vss) of Necitumumab After Single Dose [ Time Frame: Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion ]
    Vss is that amount of plasma in which the study drug needs to be dissolved to attain a steady state drug concentration. Vss was not analyzed for participants in Cohorts 1 and 3 as Vss is derived from AUC (0-∞). AUC(0-∞) was calculated only for participants in Cohort 2 as the percentage of AUC extrapolated beyond tlast was greater than 30% for the remaining participants.

  • PK: Vss of Necitumumab After Multiple Doses [ Time Frame: Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion ]
    Vss is that amount of plasma in which the study drug needs to be dissolved to attain a steady state drug concentration. Data did not allow calculation of Vss for participants in Cohorts 1 and 3.


Secondary Outcome Measures:
  • Immunogenicity (IK): Number of Participants With Treatment-Emergent Anti-IMC-11F8 Antibodies [ Time Frame: For Cohorts 1, 2 and 3: Prior to first infusions of Cycles 1, 2, and 4 and at the 30-day follow-up visit (+7 days) after the last dose of study drug ]
    Treatment-emergent samples were defined as samples which showed at least 4-fold difference (2 dilution increase) at post-baseline in IK titer over the baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20).


Enrollment: 15
Study Start Date: January 2010
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 Biological: IMC-11F8
600 milligrams (mg) intravenously, Days 1 and 8 every 3 weeks
Other Names:
  • Necitumumab
  • LY3012211
Experimental: Cohort 2 Biological: IMC-11F8
800 mg intravenously, every 2 weeks
Other Names:
  • Necitumumab
  • LY3012211
Experimental: Cohort 3 Biological: IMC-11F8
800 mg intravenously, Days 1 and 8 every 3 weeks
Other Names:
  • Necitumumab
  • LY3012211

Detailed Description:

This single center, open-label, single-arm, Phase 1 study will enroll 18 participants at a maximum. The actual size will vary depending on the dose-limiting toxicities (DLTs) observed and the resultant sizes of the cohorts. Participants will receive IMC-11F8 administered intravenously, once every 2 weeks or on Days 1 and 8 every 3 weeks for 6 weeks (1 cycle). All infusions can be administered within ± 1 day of the scheduled administration date. After 1 cycle of treatment, participants who have an objective response or stable disease may continue to receive IMC-11F8 at the same dose and schedule until disease progression or other withdrawal criteria are met.

A minimum of 3 participants will be enrolled in each cohort. Dose escalation in successive cohorts will occur once all participants complete 1 cycle of therapy.

Participants will be enrolled sequentially into each cohort. A completed participant will be either a participant who completes the initial 6-week treatment period (Cycle 1) or a participant who discontinues therapy for an IMC-11F8-related toxicity during Cycle 1. Participants who do not complete the first 6 weeks of treatment for reasons other than an IMC-11F8-related toxicity will be replaced. Toxicity data for each cohort will be reviewed prior to dose escalation. Upon completion of all required safety evaluations during the initial 6 weeks, the next cohort of new participants will be treated at the next higher dose level using a dose escalation scheme.

  Eligibility

Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Solid tumor participant who has been histopathologically or cytologically documented
  • Advanced primary or recurrent solid tumors participant who has not responded to standard therapy or for whom no standard therapy is available
  • The participant has measurable or nonmeasurable lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 guidelines
  • The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1 at study entry
  • The participant is able to provide written informed consent
  • The participant is age 20 years or older
  • The participant has a life expectancy of > 3 months
  • The participant has adequate hematologic function
  • The participant has adequate renal function
  • The participant agrees to use adequate contraception for the duration of study participation and for at least 12 weeks after the last dose of study therapy
  • The participant has adequate recovery from recent surgery, chemotherapy, and radiation therapy (including palliative radiation therapy). At least 28 days (6 weeks for nitrosoureas or mitomycin C) must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. For treatment with nonapproved monoclonal antibodies, a minimum of 8 weeks must have elapsed
  • The participant is willing to comply with study procedures until the End-of-Therapy visit

Exclusion Criteria:

  • The participant has received chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or the participant has ongoing side effects ≥Grade 2 due to agents administered more than 28 days earlier (except alopecia)
  • The participant has documented and/or symptomatic brain or leptomeningeal metastases (participants who are clinically stable [no symptoms during the 4 weeks prior to enrollment] with an assessment that no further treatment [radiation, surgical excision, or administration of steroids] is required are permitted to enter the study)
  • The participant has an uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection requiring systemic antibiotic treatment
    • Congestive heart failure (Class III or IV per the New York Heart Association heart disease classification guidelines)
  • The participant has participated in clinical studies of nonapproved experimental agents or procedures within 4 weeks prior to first dose of study therapy, or within 8 weeks prior to first dose of study therapy for nonapproved monoclonal antibodies
  • The participant has received any previous treatment with monoclonal antibodies targeting the epidermal growth factor receptor (EGFR). Previous treatment with EGFR tyrosine kinase inhibitors (TKI), approved or nonapproved, is allowed. There must be a time interval of at least 4 weeks between the last EGFR TKI dose and the first dose of IMC-11F8
  • The participant has acute or subacute intestinal occlusion/obstruction
  • The participant has a history of inflammatory bowel disease (for example, Crohn's disease, ulcerative colitis) requiring medical intervention in the 3 years prior to study entry
  • The participant has acute pulmonary disorder, interstitial pneumonia, pulmonary fibrosis, or history thereof
  • The participant has a known allergy to any of the treatment components, or to monoclonal antibodies or other therapeutic proteins such as fresh frozen plasma, human serum albumin, cytokines, or interleukins. In the event that there is suspicion that the participant may have allergies, the participant should be excluded
  • The participant, if female, is pregnant (confirmed by urine or serum pregnancy test) or lactating
  • The participant has known alcohol or drug dependency
  • The participant is hepatitis B virus (HBV) antigen, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody positive
  • The participant is assessed as inadequate for the study by the investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01088464

Locations
Japan
ImClone Investigational Site
Tokyo, Japan, 104-0045
Sponsors and Collaborators
Eli Lilly and Company
Parexel
Investigators
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
  More Information

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01088464     History of Changes
Other Study ID Numbers: 13904
CP11-0907 ( Other Identifier: ImClone Systems )
I4X-IE-JFCA ( Other Identifier: Eli Lilly )
21-1901 ( Other Identifier: PMDA (MoH) in Japan )
Study First Received: March 16, 2010
Results First Received: December 21, 2015
Last Updated: December 9, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.

This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.


Keywords provided by Eli Lilly and Company:
Human Immunoglobulin Gamma-1 (IgG1)
Monoclonal Antibody (MAb)
Epidermal Growth Factor Receptor (EGFR)
Advanced Solid Tumors

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 18, 2017