A Drug-Interaction Study of Necitumumab (IMC-11F8) in Combination With Gemcitabine-Cisplatin

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01606748
First received: May 24, 2012
Last updated: July 15, 2016
Last verified: July 2016

May 24, 2012
July 15, 2016
August 2012
June 2013   (final data collection date for primary outcome measure)
  • Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Necitumumab [ Time Frame: Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 Hour (h) Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion ] [ Designated as safety issue: No ]
  • PK: Dose-Normalized Cmax of Gemcitabine [ Time Frame: Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion ] [ Designated as safety issue: No ]
  • PK: Dose-Normalized Cmax of Cisplatin [ Time Frame: Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion ] [ Designated as safety issue: No ]
  • PK: Area Under Concentration-Time Curve From Zero to Time 168 (AUC[-168]) of Necitumumab [ Time Frame: Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1, Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion ] [ Designated as safety issue: No ]
  • PK: Dose-Normalized AUC(0-24) of Gemcitabine [ Time Frame: Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion ] [ Designated as safety issue: No ]
  • PK: Dose-Normalized AUC(0-5) of Cisplatin [ Time Frame: Run-In Period Day 1 Cohort 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion; Cycle 1, Day 1: 0, 2, 2.03, 2.25, 3, 3.67 and 5.67 h Post Start of Infusion ] [ Designated as safety issue: No ]
  • PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity, (AUC[0-∞]) of Necitumumab [ Time Frame: Run-In Period Day 3 Cohort 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion; Cycle 1 Day 1: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion ] [ Designated as safety issue: No ]
  • PK: Dose Normalized AUC(0-∞) of Gemcitabine [ Time Frame: Run-In Period Day 1 Cohort 1: 0,0.5,1,1.5,3,4,6.67 and 24h Post Start of Infusion; Cycle 1, Day 1: 0, 0.50, 1, 1.5, 3, 4.67, 6.67 and 24 h Post Start of Infusion ] [ Designated as safety issue: No ]
  • Pharmacokinetics: maximum observed drug concentration (Cmax) of necitumumab, gemcitabine, and cisplatin [ Time Frame: PK Run-in Period and Treament Period: Predose, up to 168 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics: area under concentration-time curve [AUC(0-t)] of necitumumab, gemcitabine, and cisplatin [ Time Frame: PK Run-in Period and Treament Period: Predose, up to 168 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics: area under the plasma concentration-time curve from time zero to infinity [AUC(0-∞)] of gemcitabine and cisplatin [ Time Frame: PK Run-in Period and Treament Period: Predose, up to 168 hours post dose ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01606748 on ClinicalTrials.gov Archive Site
  • Number of Participants With Anti-Necitumumab Antibodies [ Time Frame: Baseline through, 30-Day Follow-Up ] [ Designated as safety issue: No ]
    A participant was considered to have an anti-necitumumab antibody response if anti-drug antibodies (ADA) were confirmed positive. Treatment emergent antibodies were defined as any anti-necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer.
  • Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) (Antitumor Activity of Necitumumab in Combination With Gemcitabine-cisplatin Chemotherapy) [ Time Frame: Baseline to Measured Progressive Disease (Up to 14 Months) ] [ Designated as safety issue: No ]
    ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, CR was defined as the disappearance of all target and non-target lesions; PR defined as a >30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD. Percentage of participants was calculated as: (total number of participants with CR or PR from start of the treatment until disease progression or recurrence)/total number of participants treated) * 100.
  • PK: Cmax of Necitumumab After Administration of Process C and Process D Drug Product [ Time Frame: Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion ] [ Designated as safety issue: No ]
  • PK: AUC(0-∞) of Necitumumab After Administration of Process C and Process D Drug Product [ Time Frame: Run-In Period Day 3 Cohort 1 and Cohort 2: 0, 0.83, 1.33, 1.83, 3.83, 7.5, 24.83, 72 and 168 h Post Start of Infusion ] [ Designated as safety issue: No ]
  • Incidence of anti-necitumumab antibodies [ Time Frame: Pretreatment, Day 1 of Cycle 1, 2, 4 and 6, and at 30-day follow-up ] [ Designated as safety issue: No ]
  • Antitumor activity of necitumumab in combination with gemcitabine-cisplatin chemotherapy (tumor response evaluated per the Response Evaluation Criteria in Solid Tumors, Version 1.1 [RECIST 1.1]) [ Time Frame: Every 6 weeks post first dose ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Drug-Interaction Study of Necitumumab (IMC-11F8) in Combination With Gemcitabine-Cisplatin
An Open-Label, Non-controlled, Non-randomized Sequential Design, Drug-Interaction Study of Necitumumab (IMC-11F8) in Combination With Gemcitabine-Cisplatin in Patients With Advanced Solid Cancers
The purpose of this study is to investigate the pharmacokinetics (PK) of necitumumab in combination with gemcitabine-cisplatin in participants with advanced malignant solid tumors and to assess the potential for drug-drug interactions between necitumumab and gemcitabine-cisplatin.
Not Provided
Interventional
Phase 2
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Malignant Solid Tumor
  • Biological: Necitumumab

    PK Run-In Period: Necitumumab administered on Day 3 of the 3-week PK run-in period as an intravenous (I.V.) infusion at an absolute dose of 800 mg

    Treatment Cycles: Necitumumab administered on Days 1 and 8 of every 3-week cycle as an intravenous (I.V.) infusion at an absolute dose of 800 mg

    Participants in Cohort 1 will receive necitumumab Process C drug product and participants in Cohort 2 will receive necitumumab Process D drug product

    Other Names:
    • IMC-11F8
    • LY3012211
    • Portrazza®
  • Drug: Gemcitabine

    PK Run-In Period: Gemcitabine administered on Day 1 of the 3-week PK run-in period as an I.V. infusion at a dose of 1250 milligram per square meter (mg/m2)

    Treatment Cycles: Gemcitabine administered on Days 1 and 8 of every 3-week cycle as an I.V. infusion at a dose of 1250 mg/m2

    Other Names:
    • Gemzar®
    • LY188011
  • Drug: Cisplatin

    PK Run-In Period: Cisplatin administered on Day 1 of the 3-week PK run-in period as an I.V. infusion at a dose of 75 mg/m2

    Treatment Cycles: Cisplatin administered on Day 1 of every 3-week cycle as an I.V. infusion at a dose of 75 mg/m2

Experimental: Necitumumab, Gemcitabine and Cisplatin
The study will be conducted in two sequential periods: a 3-week PK run-in participants will be treated sequentially with single doses of cisplatin, gemcitabine, and necitumumab. Cycle 1 will begin immediately following the PK run-in period.
Interventions:
  • Biological: Necitumumab
  • Drug: Gemcitabine
  • Drug: Cisplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
June 2016
June 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Have documented advanced or metastatic malignant solid tumors (except for colorectal tumors with KRAS mutation) that are resistant to standard therapy or for which no standard therapy is available
  • May have measurable or non-measurable disease
  • Have resolution to Grade 0 or 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE 4.0) of all clinically significant toxic effects (other than alopecia) of prior chemotherapy, surgery, radiotherapy, or hormonal therapy
  • Have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
  • Have adequate hepatic, hematologic and renal function
  • If female, are surgically sterile, postmenopausal, or agree to be compliant with a highly effective contraceptive method during and for 6 months after the treatment period. If male, are surgically sterile or agree to be compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period
  • Female participants of childbearing potential have a negative serum pregnancy test within 7 days prior to the first dose of study therapy

Exclusion Criteria:

  • Have received a systemic anticancer agent (including EGFR tyrosine kinase inhibitors) or device within 28 days prior to first dose of study therapy
  • The most recent anticancer therapy received by the participant included either gemcitabine or cisplatin (or both)
  • Have received radiotherapy within 14 days prior to first dose of study therapy
  • Have received cytotoxic chemotherapy within 21 days prior to first dose of study therapy
  • Are receiving concurrent treatment with another anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiation therapy, chemoembolization, or targeted therapy
  • Are considered surgical candidates (with resectable disease)
  • Have brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants
  • Have narrowing of or blockage in large veins
  • Have coronary artery disease or uncontrolled congestive heart failure
  • Have uncontrolled angina pectoris, or experienced myocardial infarction within 6 months prior to first dose of study therapy
  • Have an ongoing or active infection (requiring treatment), including active tuberculosis or known infection with the human immunodeficiency virus
  • Have a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder
  • Have known drug or alcohol abuse
  • If female, are pregnant or breastfeeding
  • Have had major surgery within 28 days prior to first dose of study medication or subcutaneous venous access device implantation within 7 days prior to first dose of study therapy
  • Are currently enrolled in, or discontinued within the 30 days prior to first dose of study therapy from a clinical trial involving an investigational product or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01606748
14473, CP11-1115, I4X-IE-JFCJ
No
Not Provided
Not Provided
Eli Lilly and Company
Eli Lilly and Company
Not Provided
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
Eli Lilly and Company
July 2016

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