Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of IMC-1121B in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01005355
Recruitment Status : Completed
First Posted : October 30, 2009
Results First Posted : June 18, 2014
Last Update Posted : June 18, 2014
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE October 5, 2009
First Posted Date  ICMJE October 30, 2009
Results First Submitted Date  ICMJE May 16, 2014
Results First Posted Date  ICMJE June 18, 2014
Last Update Posted Date June 18, 2014
Study Start Date  ICMJE September 2009
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2014)
  • Number of Participants With Drug-Related Adverse Events [ Time Frame: Baseline to study completion up to 48 weeks ]
    Data presented are the number of participants who experienced adverse events (AE) of any grade, AE of Grade ≥3 based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v 3.0), serious adverse events (SAE) and AE resulting in death that was considered to be related to IMC-1121B (ramucirumab). A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
  • IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 1 and 2 [ Time Frame: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle ]
  • IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 3 to 5 [ Time Frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose ]
    Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated.
  • IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) Versus Time Curve - Cohorts 1 and 2 During Cycles 1 and 2 [ Time Frame: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle ]
    AUC for Cycle 1 is AUC from time zero to infinity [AUC(0-∞)] and for Cycle 2 is AUC over a dosing interval (AUCτ).
  • IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohorts 1 and 2 During Cycles 3 to 5 [ Time Frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose ]
    Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated.
  • IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohorts 1 and 2 During Cycles 1 and 2 [ Time Frame: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle ]
  • IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohorts 1 and 2 During Cycles 3 to 5 [ Time Frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose ]
    Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated.
  • IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 1 and 2 [ Time Frame: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle ]
  • IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 3 to 5 [ Time Frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose ]
    Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated.
  • IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 1 and 2 [ Time Frame: Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle ]
  • IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 3 to 5 [ Time Frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose ]
    Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated.
  • IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohort 3 During Cycles 1 and 2 [ Time Frame: Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle ]
    AUC for Cycle 1 is AUC from time zero to infinity [AUC(0-∞)] and for Cycle 2 is AUC over a dosing interval (AUCτ).
  • IMC-1121B Pharmacokinetics - Area Under the Concentration (AUC) - Cohort 3 During Cycles 3 to 5 [ Time Frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose ]
    Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated.
  • IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohort 3 During Cycles 1 and 2 [ Time Frame: Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle ]
  • IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohort 3 During Cycles 3 to 5 [ Time Frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose ]
    Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated.
  • IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 1 and 2 [ Time Frame: Day 1 and Day 22 of Cycles 1 and 2 of a 6-week cycle ]
  • IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 3 to 5 [ Time Frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour post-dose ]
    Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated.
Original Primary Outcome Measures  ICMJE
 (submitted: October 29, 2009)
  • To assess the safety of IMC-1121B of patients who fulfill the diagnostic criteria in Patients With Advanced Solid Tumors. [ Time Frame: 10 months ]
  • Pharmacokinetic parameter (PK)of IMC-1121B, Cmax. [ Time Frame: 10 months ]
  • Pharmacokinetic parameter (PK)of IMC-1121B, AUC0-inf. [ Time Frame: 10 months ]
  • Pharmacokinetic parameter (PK)of 1121B, t½. [ Time Frame: 10 months ]
  • Pharmacokinetic parameter (PK)of IMC-1121B,Vss. [ Time Frame: 10 months ]
Change History Complete list of historical versions of study NCT01005355 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2014)
Screen for the Development of Circulating Antibodies Against IMC-1121B (Immunogenicity) [ Time Frame: Baseline to study completion up to 48 weeks ]
Data presented are the number of participants with treatment emergent antibody positive.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 29, 2009)
Screen for the development of circulating antibodies against IMC-1121B (immunogenicity). [ Time Frame: 10 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of IMC-1121B in Patients With Advanced Solid Tumors
Official Title  ICMJE Phase 1 Study of IMC-1121B in Patients With Advanced Solid Tumors
Brief Summary This trial is testing the investigational drug IMC-1121B administered to Japanese participants with advanced solid tumors who have not responded to standard therapy or for whom no standard therapy is available. The rationale for performing this trial is to establish the safety profile and the pharmacokinetics of IMC-1121B.
Detailed Description

This single center, open-label, single-arm, Phase 1 study will enroll approximately 15 to 18 participants. The actual size will vary depending on the dose-limiting toxicities (DLTs) observed and the resultant sizes of the cohorts. Participants will receive IMC-1121B, administered intravenously, once every 2 or 3 weeks for 6 weeks (one cycle). After one cycle of treatment, participants who have an objective response or stable disease may continue to receive IMC-1121B at the same dose and schedule until disease progression or other withdrawal criteria are met. A minimum of three participants will be enrolled in each cohort. Dose escalation in successive cohorts will occur once all participants complete one 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-1121B related toxicity during Cycle 1. Participants who do not complete the first 6 weeks of treatment for reasons other than an IMC-1121B -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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE Biological: IMC-1121B
Cycle 1: Upon completion of enrollment criteria confirmed at screening, the first dose of study medication should be administered within 7 days. The infusion will be planned every 2 weeks or every 3 weeks on the same day of the week of the first infusion. Dose escalation to Cohort 2 may occur in the absence of a dose-limiting toxicity (DLT) in the first three participants treated in Cohort 1 during the initial 6-week dosing period (Cycle 1). The same procedure will be followed for dose escalation from Cohort 2 to Cohort 3. If 1 of 3 participants in any cohort experiences a DLT in the first 6 weeks (Cycle 1), 3 additional participants will be enrolled in that cohort. Dose escalation to the next cohort may occur if less that 2 of 6 participants experience a DLT during Cycle 1.
Other Names:
  • RAMUCIRUMAB
  • LY3009806
Study Arms  ICMJE Experimental: IMC-1121B
Participants receiving IMC-1121B intravenously
Intervention: Biological: IMC-1121B
Publications * Nokihara H, Yamamoto N, Yamada Y, Honda K, Asahina H, Tamura Y, Hozak RR, Gao L, Suzukawa K, Enatsu S, Tamura T. A phase 1 study of ramucirumab in Japanese patients with advanced solid tumors. Jpn J Clin Oncol. 2017 Apr 1;47(4):298-305. doi: 10.1093/jjco/hyx008.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 14, 2013)
15
Original Estimated Enrollment  ICMJE
 (submitted: October 29, 2009)
18
Actual Study Completion Date  ICMJE February 2011
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Solid tumor participant who was been histopathologically or cytologically documented.
  • Advanced primary or recurrent solid tumors participant who has not responded to standard therapy or no standard therapy is available.
  • The participant has measurable or nonmeasurable lesions according to Response Evaluation Criteria in Solid Tumors (RECIST).
  • The participant has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1 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, as defined by:
  • An absolute neutrophil count (ANC) > 1500/cubic millimeter (mm³) or /microliter (µL)
  • A hemoglobin level > 10 grams/deciliter (g/dL)
  • A platelet count > 100,000/mm³ or /µL
  • The participant has adequate hepatic function, as defined by:
  • A total bilirubin level < 1.8 milligrams/deciliter (mg/dL)
  • Aspartate transaminase (AST) levels < 86 International Units/liter (IU/L)
  • Alanine transaminase (ALT) levels ≤ 86 IU/L
  • The participant has adequate renal function, as defined by:
  • Serum creatinine level ≤ 1.5 mg/dL, or
  • Calculated serum creatinine clearance (Cockcroft-Gault) ≥ 60 milliliters/minute (mL/min)
  • The participant's urinary protein is 0 on dipstick or 1+ but participant does not have edema nor serum albumin < lower level of normal (LLN).
  • The participant has adequate coagulation function, as defined by international normalized ratio (INR) ≤ 1.5.
  • The participant agrees to use adequate contraception during the study period and for 12 weeks after the last dose of study treatment.

Exclusion Criteria:

  • The participant has had chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or participant has ongoing side effects ≥ Grade 2 due to agents administered more than 28 days earlier.
  • The participant has obvious evidence of intratumor cavitation.
  • The participant has undergone major surgery (example, laparotomy, thoracotomy, removal of organ[s]) within 28 days prior to study entry, or subcutaneous venous access device placement within 7 days prior to study entry.
  • The participant has a history of postoperative bleeding complications or wound complications from a surgical procedure.
  • The participant has elective or planned surgery to be conducted during the trial.
  • The participant has documented and/or symptomatic brain or leptomeningeal metastases. (Participants who are clinically stable [no symptoms during 4 weeks prior to the enrollment] with an assessment that no further treatment [radiation, surgical excision, and administration of steroids] is required, are permitted to enter the study.)
  • The participant has uncontrolled intercurrent illness including, but not limited to:
  • Thrombotic or hemorrhagic disorders
  • Hemoptysis (approximately one-half of a teaspoon)
  • Ongoing or active infection requiring systemic antibiotic treatment
  • Congestive heart failure (Class III or IV of the New York Heart Association classification for heart disease)
  • Angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
  • Uncontrolled hypertension (systolic blood pressure > 150 millimeters of mercury (mmHg), diastolic blood pressure > 95 mm Hg)
  • Cardiac arrhythmia requires treatment [National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v 3.0), Grade 3], or asymptomatic sustained ventricular tachycardia)
  • Peripheral neuropathy of any etiology ≥ Grade 2 (NCI-CTCAE v 3.0)
  • The participant has participated in clinical studies of non-approved experimental agents or procedures within 4 weeks prior to study entry for small molecules, or 8 weeks prior to study entry for non-approved monoclonal antibodies.
  • The participant, if female, is pregnant (confirmed by urine or serum pregnancy test) or lactating.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01005355
Other Study ID Numbers  ICMJE 13898
CP12-0816 ( Other Identifier: ImClone Systems )
I4T-IE-JVBI ( Other Identifier: Eli Lilly and Company )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Parexel
Investigators  ICMJE
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
PRS Account Eli Lilly and Company
Verification Date May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP