Overview

This trial is active, not recruiting.

Condition solid tumor
Treatments cetuximab, cisplatin, 5 - fluorouracil
Phase phase 2
Target EGFR
Sponsor Eli Lilly and Company
Start date April 2010
End date October 2015
Trial size 8 participants
Trial identifier NCT01099358, 13418, I4E-MC-JXBA

Summary

The primary purpose of this study is to help answer the following research question(s):

- To see how the body absorbs, processes, and gets rid of cetuximab when the drug is taken in combination with cisplatin [pharmacokinetic (PK) analysis]

- To see if any drug interactions occur between cetuximab and cisplatin.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification pharmacokinetics/dynamics study
Intervention model single group assignment
Masking open label
Arm
(Experimental)
Cycle 1 (1 week, combination therapy): Cetuximab 400 milligrams per square meter (mg/m^2) on day 1; Cisplatin 100 mg/m^2 on day 1; optional 5- fluorouracil (FU) 1000 mg/ m^2 on day 1-4. After 1 cycle, participants may continue treatment as determined by the physician until progression of disease, unacceptable toxicity, or another withdrawal criterion is met. After protocol amendment June 2014, any newly enrolled participants will be placed into Cetuximab and Cisplatin (D) arm only.
cetuximab
Administered Intravenously
cisplatin
Administered Intravenously
5 - fluorouracil
Administered Intravenously
(Experimental)
Cycle 1 (4 weeks, combination therapy): Week 1 - Cisplatin 100 mg/m^2 on day 1; 5-FU 1000 mg/m^2 on days 1-4. Week 2 - Cetuximab 400 mg/m^2 on day 1. Week 3 - Cetuximab 250 mg/m^2 on day 1. Week 4 - Cetuximab 250 mg/m^2 on day 1. Cycle 2-6 (3 weeks combination therapy): Week 1 - Cisplatin 100 mg/m^2 on day 1; 5-FU 1000 mg/m^2 on days 1-4; Cetuximab 250 mg/m^2 on day 1. Week 2 - Cetuximab 250 mg/m^2 on day 1. Week 3 - Cetuximab 250 mg/m^2 on day 1. After 6 cycles, participants may then receive weekly Cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met. Due to protocol amendment in September 2011, any newly enrolled participants were placed into Cetuximab and Cisplatin (C) arm only. After protocol amendment June 2014, any newly enrolled participants will be placed into Cetuximab and Cisplatin (D) arm only.
cetuximab
Administered Intravenously
cisplatin
Administered Intravenously
5 - fluorouracil
Administered Intravenously
(Experimental)
Cycle 1: Week 1 - Cisplatin 100 mg/m^2; 5-FU 1000 mg/m^2 on days 1-4 Week 2 - Cetuximab 400 mg/m^2 on day 1 Week 3 - Cetuximab 250 mg/m^2 on day 1. Cycle 2-6: Week 1 - Cisplatin 100 mg/m^2; 5-FU 1000 mg/m^2 on days 1-4; Cetuximab 250 mg/m^2 on day 1. Week 2 - Cetuximab 250 mg/m^2 on day 1. Week 3 - Cetuximab 250 mg/m^2 on day 1. After 6 cycles, participants may then receive weekly Cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met. Due to protocol amendment in September 2011, any newly enrolled participants were placed into Cetuximab and Cisplatin (C) arm only. After protocol amendment June 2014, any newly enrolled participants will be placed into Cetuximab and Cisplatin (D) arm only.
cetuximab
Administered Intravenously
cisplatin
Administered Intravenously
5 - fluorouracil
Administered Intravenously
(Experimental)
Cycle 1: Week 1 - Cetuximab 400 mg/m^2 on day 1 Week 2 - Cetuximab 250 mg/m^2 on day 1 Week 3 - Cetuximab 250 mg/m^2 on day 1. Cycle 2-7: Week 1 - Cisplatin 100 mg/m^2; 5-FU 1000 mg/m^2 on days 1-4; Cetuximab 250 mg/m^2 on day 1. Week 2 - Cetuximab 250 mg/m^2 on day 1. Week 3 - Cetuximab 250 mg/m^2 on day 1. After 7 cycles, participants may then receive weekly Cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met. Due to protocol amendment in September 2011, any newly enrolled participants were placed into Cetuximab and Cisplatin (C) arm only. After protocol amendment June 2014, any newly enrolled participants will be placed into Cetuximab and Cisplatin (D) arm only.
cetuximab
Administered Intravenously
cisplatin
Administered Intravenously
5 - fluorouracil
Administered Intravenously

Primary Outcomes

Measure
Cisplatin pharmacokinetics: Area under the curve (AUC)
time frame: Baseline (prior to Cisplatin infusion); 1, 1:30, 2, 3, 5, 8, 24, 72 hours (after the start of Cisplatin infusion) on Day 1 of weeks 1 (Groups C and D) and 5 (Group C)
Cetuximab pharmacokinetics: Area under the curve (AUC)
time frame: Baseline (prior to Cetuximab infusion); 1, 2, 4, 8, 24, 72, 120, and 168 hours (after the start of Cetuximab infusion) on Day 1 of weeks 4 and 5 (Group C)
Cisplatin pharmacokinetics: Maximum plasma concentration (Cmax)
time frame: Baseline (prior to Cisplatin infusion); 1, 1:30, 2, 3, 5, 8, 24, 72 hours (after the start of Cisplatin infusion) on Day 1 of weeks 1 (Groups C and D) and 5 (Group C)
Cetuximab pharmacokinetics: Maximum plasma concentration (Cmax)
time frame: Baseline (prior to Cetuximab infusion); 1, 2, 4, 8, 24, 72, 120, and 168 hours (after the start of Cetuximab infusion) on Day 1 of weeks 4 and 5 (Group C)
Cisplatin pharmacokinetics: Measurement of the time after administration when the maximum plasma concentration is reached (Tmax)
time frame: Baseline (prior to Cisplatin infusion); 1, 1:30, 2, 3, 5, 8, 24, 72 hours (after the start of Cisplatin infusion) on Day 1 of weeks 1 (Groups C and D) and 5 (Group C)
Cetuximab pharmacokinetics: Measurement of the time after administration when the maximum plasma concentration is reached (Tmax)
time frame: Baseline (prior to Cetuximab infusion); 1, 2, 4, 8, 24, 72, 120, and 168 hours (after the start of Cetuximab infusion) on Day 1 of weeks 4 and 5 (Group C)
Cetuximab pharmacokinetics: Confirmatory serum concentration
time frame: Prior to Cisplatin infusion on Day 1 of week 1 (Group D)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - The participant has histologically or cytologically advanced solid tumor that is resistant to standard therapy or for which there is no standard therapy. - The participant has measurable or non-measurable disease. - The participant has a life expectancy of greater than 3 months. - The participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. - The participant has adequate hematologic function as defined by absolute neutrophil count greater than or equal to 1500/microliter (μL), hemoglobin greater than or equal to 9 grams/deciliter (g/dL), and platelet count greater than or equal to 100,000/μL. - The participant has adequate hepatic function as defined by a total bilirubin less than or equal to 2 x the upper limit of normal (ULN), aspartate transaminase (AST, SGOT) and alanine transaminase (ALT, SGPT) less than or equal to 3 x the ULN (or less than or equal to 5 x the ULN in the presence of known liver metastases). - The participant has adequate renal function as defined by serum creatinine less than or equal to 1.5 x the institutional ULN or creatinine clearance greater than or equal to 60 mL/min for participants with creatinine levels above the ULN. - The participant has the ability to understand, and the willingness to sign, a written informed consent document. - If the participant has received prior therapy with platinum, the time to the first treatment of study drug from the last platinum exposure is >28 days. Exclusion Criteria: - The participant has symptomatic brain or leptomeningeal metastasis. - The participant has not recovered from Adverse Events due to agents administered more than 4 weeks earlier. Neurotoxicity, if present, must have improved to Grade less than 2 per the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 3.0. - The participant is receiving any other investigational agent(s). - The participant is receiving concurrent treatment with other anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, RT, chemoembolization, or targeted therapy. Participants receiving palliative radiation therapy to bony metastases prior to the first dose of study medication are eligible. - The participant is receiving therapy with immunosuppressive agents. - The participant has known drug or alcohol abuse. - The participant has uncontrolled hypertension defined as systolic blood pressure greater than or equal to 180 millimeters of mercury (mm Hg) or diastolic blood pressure greater than or equal to 130 mm Hg. - The participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab or cisplatin. - The participant has a medical or psychological condition that would not permit the participant to complete the study or sign informed consent. - The participant has clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency. - The participant, if female, is pregnant (confirmed by serum or urine beta-human chorionic gonadotropin [β-HCG] pregnancy test) or breastfeeding - The participant has had a known positive test result for the human immunodeficiency virus. - The participant has an active infection (requiring intravenous [IV] antibiotics), including tuberculosis.

Additional Information

Official title Phase 2 Study to Evaluate the Pharmacokinetics and Drug-Drug Interaction of Cetuximab and Cisplatin in Patients With Advanced Solid Tumors
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.
Location data was received from the National Cancer Institute and was last updated in February 2016.