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
Results First Received: December 21, 2015  
Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Malignant Solid Tumor
Interventions: Biological: Necitumumab
Drug: Gemcitabine
Drug: Cisplatin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Cohort 1 'completers' completed the PK run-in period (3 Weeks) and Cycle 1, Day 1 and Cohort 2 'completers' completed the PK run-in period.

Reporting Groups
  Description
Necitumumab Cohort 1

Necitumumab administered on Day 3 of the 3-week PK run-in period as an intravenous (IV) infusion at an absolute dose of 800 milligrams (mg). Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg.

Participants in Cohort 1 received necitumumab Process C drug product. Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/square meter (m2).

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

Necitumumab Cohort 2

Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg.

Participants in Cohort 2 received necitumumab drug product manufactured using a new and comparable necitumumab drug substance (Process D drug product).

Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2.

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


Participant Flow:   Overall Study
    Necitumumab Cohort 1     Necitumumab Cohort 2  
STARTED     18     17  
Received at Least 1 Dose of Study Drug     18     17  
COMPLETED     13     6  
NOT COMPLETED     5     11  
Adverse Event                 1                 0  
Progressive Disease                 1                 0  
Withdrawal by Subject                 1                 0  
On study treatment                 2                 11  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of study drug.

Reporting Groups
  Description
Necitumumab Cohort 1

Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg.

Participants in Cohort 1 received necitumumab Process C drug product and participants in Cohort 2 received necitumumab Process D drug product.

Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2.

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

Necitumumab Cohort 2

Necitumumab administered on Day 3 of the 3-week PK run-in period as an IV infusion at an absolute dose of 800 mg. Necitumumab administered on Days 1 and 8 of every 3-week cycle as an IV infusion at an absolute dose of 800 mg.

Participants in Cohort 1 received necitumumab Process C drug product and participants in Cohort 2 received necitumumab Process D drug product.

Gemcitabine administered on Day 1 of the 3-week PK run-in period as an IV infusion at a dose of 1250 mg/m2.

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

Total Total of all reporting groups

Baseline Measures
    Necitumumab Cohort 1     Necitumumab Cohort 2     Total  
Number of Participants  
[units: participants]
  18     17     35  
Age  
[units: years]
Mean (Standard Deviation)
  55.3  (15.54)     58.2  (13.84)     56.7  (14.59)  
Gender  
[units: participants]
     
Female     11     10     21  
Male     7     7     14  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     1     1     2  
Not Hispanic or Latino     17     16     33  
Unknown or Not Reported     0     0     0  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     1     0     1  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     0     3     3  
White     17     14     31  
More than one race     0     0     0  
Unknown or Not Reported     0     0     0  
Region of Enrollment  
[units: participants]
     
United States     18     17     35  
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline [1]
[units: participants]
     
0     9     7     16  
1     9     10     19  
>=2     0     0     0  
Disease Characteristics - Tumor Type  
[units: participants]
     
Breast Carcinoma     3     4     7  
Ovarian Carcinoma     2     1     3  
Small Cell Lung Carcinoma     2     1     3  
Thymic Tumor     2     0     2  
Nonsmall Cell Lung Carcinoma     2     0     2  
Melanoma     1     1     2  
Head and Neck Carcinoma     1     1     2  
Endometrial Carcinoma     1     1     2  
Hepatobilliary Carcinoma     1     0     1  
Left Parotid     1     0     1  
Liver     1     0     1  
Granulosa Cell Tumor of the Ovary     1     0     1  
Mesothelioma     0     1     1  
Neuroendocrine Tumor     0     1     1  
Hepatocellular Carcinoma     0     1     1  
Esophageal Carcinoma     0     1     1  
Colorectal Carcinoma     0     1     1  
Sarcoma, soft tissue     0     1     1  
Adenocarcinoma of the Ampula of Vater     0     1     1  
Pancreatic Carcinoma     0     1     1  
Prior Anti-Cancer Therapy [2]
[units: participants]
     
Any Prior Radiotherapy     13     10     23  
Any Prior (Adjuvant/Neoadjuvant) Systemic Therapy     17     16     33  
[1] Classifies participants according to their functional impairment. Scores range from 0 (Fully Active) to 5 (Death). 0 - Fully Active. 1 - Ambulatory, Restricted Strenuous Activity. 2 - Ambulatory, No Work Activities. 3 - Partially Confined to Bed, Limited Self Care. 4 - Completely Disabled. 5 - Death.
[2] Not all participants received prior anti-cancer therapy.



  Outcome Measures
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1.  Primary:   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 ]

2.  Primary:   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 ]

3.  Primary:   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 ]

4.  Primary:   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 ]

5.  Primary:   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 ]

6.  Primary:   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 ]

7.  Primary:   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 ]

8.  Primary:   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 ]

9.  Secondary:   Number of Participants With Anti-Necitumumab Antibodies   [ Time Frame: Baseline through, 30-Day Follow-Up ]

10.  Secondary:   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) ]

11.  Secondary:   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 ]

12.  Secondary:   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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979



Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01606748     History of Changes
Other Study ID Numbers: 14473
CP11-1115 ( Other Identifier: ImClone Systems )
I4X-IE-JFCJ ( Other Identifier: Eli Lilly and Company )
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