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
  Purpose
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.

Condition Intervention Phase
Malignant Solid Tumor
Biological: Necitumumab
Drug: Gemcitabine
Drug: Cisplatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 35
Study Start Date: August 2012
Study Completion Date: June 2016
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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


  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01606748

Locations
United States, Arizona
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.
Scottsdale, Arizona, United States, 85258
United States, Michigan
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.
Detroit, Michigan, United States, 48202
United States, Nevada
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.
Las Vegas, Nevada, United States, 89169
United States, Pennsylvania
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.
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Eli Lilly and Company
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: NCT01606748     History of Changes
Other Study ID Numbers: 14473  CP11-1115  I4X-IE-JFCJ 
Study First Received: May 24, 2012
Results First Received: December 21, 2015
Last Updated: July 15, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Advanced Malignant Solid Tumors
Solid Cancers
Non-small Cell Lung Cancer
NSCLC
Breast Cancer

Additional relevant MeSH terms:
Neoplasms
Gemcitabine
Cisplatin
Antibodies, Monoclonal
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 29, 2016