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

Phase 2

Completed

• Conditions: Malignant Solid Tumor
• Interventions: Biological: Necitumumab; Drug: Gemcitabine; Drug: Cisplatin

• Registration Number: NCT01606748
• Lead Sponsor: Eli Lilly and Company

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-05-24
• Study First Submitted QC: 2012-05-24
• Study First Posted: 2012-05-28
• Study Start: 2012-08
• Primary Completion: 2013-06
• Disposition First Submitted: 2014-04-25
• Disposition First Submitted QC: 2014-04-25
• Disposition First Posted: 2014-05-13
• Results First Submitted: 2015-12-21
• Study Completion: 2016-06
• Results First Submitted QC: 2016-07-15
• Results First Posted: 2016-08-26
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-10
• Last Update Posted: 2019-09-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Necitumumab, Gemcitabine and Cisplatin	Necitumumab	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.
Necitumumab, Gemcitabine and Cisplatin	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.
Necitumumab, Gemcitabine and Cisplatin	Gemcitabine	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.

Primary Outcome Measures

Name	Time	Method
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: 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
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 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: 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: 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(0-5) 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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Anti-Necitumumab Antibodies	Baseline through, 30-Day Follow-Up	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.
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
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)	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: 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

Trial Locations

Locations (1)

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