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

NCT01606748 | Completed Phase 2 Results

• 3 other identifiers: 14473CP11-1115I4X-IE-JFCJ
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Malignant Solid Tumor

Keywords

Advanced Malignant Solid Tumors; Solid Cancers; Non-small Cell Lung Cancer; NSCLC; Breast Cancer

Outcome Measures

Primary Outcomes (8)

• Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Necitumumab

  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

• PK: Dose-Normalized Cmax of Gemcitabine

  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

• PK: Dose-Normalized Cmax of Cisplatin

  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

• PK: Area Under Concentration-Time Curve From Zero to Time 168 (AUC[-168]) of Necitumumab

  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

• PK: Dose-Normalized AUC(0-24) of Gemcitabine

  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

• PK: Dose-Normalized AUC(0-5) of Cisplatin

  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

• PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity, (AUC[0-∞]) of Necitumumab

  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

• PK: Dose Normalized AUC(0-∞) of Gemcitabine

  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

Secondary Outcomes (4)

• Number of Participants With Anti-Necitumumab Antibodies

  Baseline through, 30-Day Follow-Up

• 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)

  Baseline to Measured Progressive Disease (Up to 14 Months)

• PK: Cmax of Necitumumab After Administration of Process C and Process D Drug Product

  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

• PK: AUC(0-∞) of Necitumumab After Administration of Process C and Process D Drug Product

  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

Study Arms (1)

Necitumumab, Gemcitabine and Cisplatin

EXPERIMENTAL

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; Drug: Gemcitabine; Drug: Cisplatin

Interventions

Necitumumab BIOLOGICAL

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

Also known as: IMC-11F8, LY3012211

Necitumumab, Gemcitabine and Cisplatin

Gemcitabine DRUG

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

Also known as: Gemzar®, LY188011

Necitumumab, Gemcitabine and Cisplatin

Cisplatin DRUG

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

Necitumumab, Gemcitabine and Cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (4)

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, 85258, United States

Location

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, 48202, United States

Location

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, 89169, United States

Location

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, 15213, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Breast Neoplasms

Interventions

necitumumab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2012
• First Posted: May 28, 2012
• Study Start: August 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2016
• Last Updated: September 30, 2019
• Results First Posted: August 26, 2016

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

US (4)