A Study in Advanced Solid Tumors

Phase 2

Completed

Conditions: Solid Tumor

Interventions: Drug: Cetuximab
Drug: Carboplatin
Drug: 5 - FU

Registration Number: NCT01063075

Lead Sponsor: Eli Lilly and Company

Brief 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 carboplatin \[pharmacokinetic (PK) analysis\]

* To see if any drug interactions occur between cetuximab and carboplatin.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 34

Inclusion Criteria

The participant has histologically or cytologically confirmed 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 according to RECIST 1.0 guidelines.
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,radiation 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 carboplatin.
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 I.V antibiotics), including tuberculosis.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cetuximab and Carboplatin (D)	5 - FU	Group D: Cycle 1 (1 week, combination therapy): 400 milligrams per square meter (mg/m ²) cetuximab administered intravenously (I.V) on week 1,day 1. Carboplatin area under the curve (AUC=5) administered I.V on week 1,day 1. Optional 5- fluorouracil (FU) administered as a 96-hour continuous infusion (C.I.) of 1000 mg/ m ²/day administered starting on week 1, day 1. After 1 cycle, participants may then receive cetuximab as determined by clinical exam or radiological imaging studies until progression of disease, unacceptable toxicity, or another withdrawal criterion is met. After protocol amendment February 2014, any newly enrolled participants were placed into Group D only.
Cetuximab and Carboplatin (C)	5 - FU	Group C: Cycle 1 (4 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week 1, day 1.1000 mg/m ²/day 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 400 mg/m² cetuximab administered I.V on week 2, day 1. 250 mg/m ² cetuximab administered I.V on week 3 and 4, day 1. Cycle 2-6 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week1,day1.1000 mg/m ²/d 5-FU as a 96-hour C.I. starting on week1, day1. 250 mg/m ² cetuximab administered I.V on Week 1-3, day 1. After 6 cycles, participants may then receive 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 carboplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into Group D arm only.
Cetuximab and Carboplatin (B)	5 - FU	Group B: Cycle 1 (3 weeks, single-agent cetuximab): 400 mg/m² cetuximab administered I.V on week 1, day 1. 250 mg/m ² cetuximab administered I.V on weeks 2 and 3, day 1. Cycle 2 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V week 1, day 1. 1000 mg/m ²/d 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 250 mg/m ² cetuximab administered I.V weeks 1- 3,day 1. After 6 cycles, participants may then receive 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 carboplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into Group D arm only.
Carboplatin and Cetuximab (A)	5 - FU	Group A: Cycle 1 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week 1, day 1. 1000 mg/m ²/d 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 400 mg/m ² cetuximab administered I.V on week 2, day 1. 250 mg/m ² cetuximab administered I.V on week 3, day 1. Cycle 2 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week 1, day 1. 1000 mg/m ²/d 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 250 mg/m ² cetuximab administered I.V on weeks 1- 3, day 1. After 7 cycles, participants may then receive 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 carboplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into Group D arm only.
Cetuximab and Carboplatin (D)	Carboplatin	Group D: Cycle 1 (1 week, combination therapy): 400 milligrams per square meter (mg/m ²) cetuximab administered intravenously (I.V) on week 1,day 1. Carboplatin area under the curve (AUC=5) administered I.V on week 1,day 1. Optional 5- fluorouracil (FU) administered as a 96-hour continuous infusion (C.I.) of 1000 mg/ m ²/day administered starting on week 1, day 1. After 1 cycle, participants may then receive cetuximab as determined by clinical exam or radiological imaging studies until progression of disease, unacceptable toxicity, or another withdrawal criterion is met. After protocol amendment February 2014, any newly enrolled participants were placed into Group D only.
Cetuximab and Carboplatin (D)	Cetuximab	Group D: Cycle 1 (1 week, combination therapy): 400 milligrams per square meter (mg/m ²) cetuximab administered intravenously (I.V) on week 1,day 1. Carboplatin area under the curve (AUC=5) administered I.V on week 1,day 1. Optional 5- fluorouracil (FU) administered as a 96-hour continuous infusion (C.I.) of 1000 mg/ m ²/day administered starting on week 1, day 1. After 1 cycle, participants may then receive cetuximab as determined by clinical exam or radiological imaging studies until progression of disease, unacceptable toxicity, or another withdrawal criterion is met. After protocol amendment February 2014, any newly enrolled participants were placed into Group D only.
Cetuximab and Carboplatin (C)	Cetuximab	Group C: Cycle 1 (4 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week 1, day 1.1000 mg/m ²/day 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 400 mg/m² cetuximab administered I.V on week 2, day 1. 250 mg/m ² cetuximab administered I.V on week 3 and 4, day 1. Cycle 2-6 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week1,day1.1000 mg/m ²/d 5-FU as a 96-hour C.I. starting on week1, day1. 250 mg/m ² cetuximab administered I.V on Week 1-3, day 1. After 6 cycles, participants may then receive 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 carboplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into Group D arm only.
Cetuximab and Carboplatin (C)	Carboplatin	Group C: Cycle 1 (4 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week 1, day 1.1000 mg/m ²/day 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 400 mg/m² cetuximab administered I.V on week 2, day 1. 250 mg/m ² cetuximab administered I.V on week 3 and 4, day 1. Cycle 2-6 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week1,day1.1000 mg/m ²/d 5-FU as a 96-hour C.I. starting on week1, day1. 250 mg/m ² cetuximab administered I.V on Week 1-3, day 1. After 6 cycles, participants may then receive 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 carboplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into Group D arm only.
Cetuximab and Carboplatin (B)	Cetuximab	Group B: Cycle 1 (3 weeks, single-agent cetuximab): 400 mg/m² cetuximab administered I.V on week 1, day 1. 250 mg/m ² cetuximab administered I.V on weeks 2 and 3, day 1. Cycle 2 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V week 1, day 1. 1000 mg/m ²/d 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 250 mg/m ² cetuximab administered I.V weeks 1- 3,day 1. After 6 cycles, participants may then receive 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 carboplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into Group D arm only.
Cetuximab and Carboplatin (B)	Carboplatin	Group B: Cycle 1 (3 weeks, single-agent cetuximab): 400 mg/m² cetuximab administered I.V on week 1, day 1. 250 mg/m ² cetuximab administered I.V on weeks 2 and 3, day 1. Cycle 2 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V week 1, day 1. 1000 mg/m ²/d 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 250 mg/m ² cetuximab administered I.V weeks 1- 3,day 1. After 6 cycles, participants may then receive 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 carboplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into Group D arm only.
Carboplatin and Cetuximab (A)	Cetuximab	Group A: Cycle 1 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week 1, day 1. 1000 mg/m ²/d 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 400 mg/m ² cetuximab administered I.V on week 2, day 1. 250 mg/m ² cetuximab administered I.V on week 3, day 1. Cycle 2 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week 1, day 1. 1000 mg/m ²/d 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 250 mg/m ² cetuximab administered I.V on weeks 1- 3, day 1. After 7 cycles, participants may then receive 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 carboplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into Group D arm only.
Carboplatin and Cetuximab (A)	Carboplatin	Group A: Cycle 1 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week 1, day 1. 1000 mg/m ²/d 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 400 mg/m ² cetuximab administered I.V on week 2, day 1. 250 mg/m ² cetuximab administered I.V on week 3, day 1. Cycle 2 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week 1, day 1. 1000 mg/m ²/d 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 250 mg/m ² cetuximab administered I.V on weeks 1- 3, day 1. After 7 cycles, participants may then receive 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 carboplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into Group D arm only.

Primary Outcome Measures

Name	Time	Method
Cetuximab PK: Confirmatory Serum Concentration	Group D: Prior to Carboplatin Infusion, Cycle 1, Day 1
Cetuximab PK: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss)	(Group B: Cycle 1 and Cycle 2+ ; Day 1, 8, 15 and Group C: Cycle 1, Day 8, 15 and 22; Cycle 2+, Day 1,8 and 15): Prior to Cetuximab Infusion, 1 Hour (H), 2 H, 4 H, 8 H, 24 H, 72 H, 120 H, and 168 H (after the start of Cetuximab Infusion)
Total Carboplatin PK: Maximum Observed Plasma Concentration (Cmax)	Group D: Cycle 1, Week 1, Day 1; Prior to Carboplatin Infusion, 1hour (H), 1:30 H, 2 H, 3 H, 5 H, 8 H, 24 H, 72 H (after the Start of Carboplatin Infusion)
Cetuximab PK: Maximum Observed Plasma Concentration at Steady State (Cmax,ss)	(Group B: Cycle 1 and Cycle 2+ ; Day 1, 8, 15 and Group C: Cycle 1, Day 8, 15 and 22; Cycle 2+, Day 1,8 and 15): Prior to Cetuximab Infusion, 1 Hour (H), 2 H, 4 H, 8 H, 24 H, 72 H, 120 H, and 168 H (after the start of Cetuximab Infusion)
Total Carboplatin PK: Time of Maximum Observed Plasma Concentration (Tmax)	Group D: Cycle 1, Week 1, Day 1; Prior to Carboplatin Infusion, 1hour (H), 1:30 H, 2 H, 3 H, 5 H, 8 H, 24 H, 72 H (after the Start of Carboplatin Infusion)
Total Carboplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞])	Group D: Cycle 1, Week 1, Day 1; Prior to Carboplatin Infusion, 1hour (H), 1:30 H, 2 H, 3 H, 5 H, 8 H, 24 H, 72 H (after the Start of Carboplatin Infusion)
Cetuximab PK: Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss)	(Group B: Cycle 1 and Cycle 2+ ; Day 1, 8, 15 and Group C: Cycle 1, Day 8, 15 and 22; Cycle 2+, Day 1,8 and 15): Prior to Cetuximab Infusion, 1 Hour (H), 2 H, 4 H, 8 H, 24 H, 72 H, 120 H, and 168 H (after the start of Cetuximab Infusion)

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (7): Highlands Oncology Group
🇺🇸
Fayetteville, Arkansas, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
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.
🇨🇦
Montreal, Quebec, Canada
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Portland VA Medical Center
🇺🇸
Portland, Oregon, United States
University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
University of Kansas Medical Center
🇺🇸
Fairway, Kansas, United States