A Study in Advanced Solid Tumors | NCT01063075

NCT01063075

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
I4E-MC-JXBB	Other Identifier	Eli Lilly and Company

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cetuximab and Carboplatin (D)	Experimental	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.	Drug: Cetuximab Drug: Carboplatin Drug: 5 - FU
Cetuximab and Carboplatin (C)	Experimental	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.	Drug: Cetuximab Drug: Carboplatin Drug: 5 - FU
Cetuximab and Carboplatin (B)	Experimental	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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Cetuximab	Drug	Administered Intravenously	Carboplatin and Cetuximab (A) Cetuximab and Carboplatin (B) Cetuximab and Carboplatin (C) Cetuximab and Carboplatin (D)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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: 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)
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)

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Highlands Oncology Group		Fayetteville	Arkansas	72703	United States
University of Kansas Medical Center

Arm/Group Information

ID	Title	Description
FG000	Carboplatin and Cetuximab (A)	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 milligrams per square meter (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.
FG001	Cetuximab and Carboplatin (B)	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.
FG002	Cetuximab and Carboplatin (C)	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.
FG003	Cetuximab and Carboplatin (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.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	All Participants (Group A, B, C and D)	Group D: Cycle 1:400 mg/m² cetuximab week (w) 1,day(d) 1.Carboplatin(AUC=5) on w 1, d 1.Optional 1000 mg/m²/d 5-FU given as a 96-hour C.I. starting(strt) on w 1, d 1. Group C: Cycle 1:Carboplatin(AUC=5) on w 1,d 1. 400 mg/m² cetuximab on w 2, d 1.Cetuximab 250 mg/m ² on w 3 and 4, d 1. Cycle 2-6:Carboplatin(AUC=5) and 250 mg/m² cetuximab on w 1, d 1.1000 mg/m²/d 5-FU given as a 96-hour C.I. strt on w 1, d 1.250 mg/m² cetuximab on w 2 and 3, d 1. Group B: Cycle 1:400 mg/m² cetuximab on w 1, d 1. 250 mg/m ² cetuximab on w 2 and 3, d 1. Cycle 2:Carboplatin(AUC=5) w 1, d 1.1000 mg/m ²/d 5-FU given as 96-hour C.I. strt on w 1, d 1. 250 mg/m ² cetuximab w 1- 3, d 1. Group A: Cycle 1:Carboplatin(AUC=5) on w 1, d 1. 1000 mg/m²/d 5-FU given as 96-hour C.I. strt on w 1, d 1. 400 mg/m² cetuximab on w 2, d 1 and 250 mg/m² cetuximab on w 3, d 1. Cycle 2:Carboplatin(AUC=5) given I.V on w 1, d 1.1000 mg/m²/d 5-FU given as 96-hour C.I. strt on w 1, d 1. 250 mg/m² cetuximab on w 1-3, d 1.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Total Carboplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞])

Participants who received at least 1 dose of study drug who were enrolled in Group(Grp)D & had evaluable PK data.Study design by intent did not collect data from Grp B.Due to participant recruitment & retention challenges,there were no PK study completers for Grp A & C.Participant recruitment & retention addressed by amending protocol to add Grp D.

Posted

Geometric Mean

Geometric Coefficient of Variation

micrograms*hour/milliliters (μg•h/mL)

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)

ID	Title	Description
OG000	Cetuximab and Carboplatin (D)	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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Carboplatin and Cetuximab (A)	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.

ID	Term
D006258	Head and Neck Neoplasms
D002277	Carcinoma
D012509	Sarcoma

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins

ID	Term
D000068818	Cetuximab
D016190	Carboplatin
D005472	Fluorouracil