Study in Advanced Solid Tumors | NCT01099358

NCT01099358

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-JXBA	Other Identifier	Eli Lilly and Company

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cetuximab and Cisplatin (D)	Experimental	Cycle 1 (1 week, combination therapy): 400 milligrams per square meter (mg/m²) cetuximab administered (admin) intravenously (I.V) on week 1, day 1. 100 mg/m² cisplatin administered I.V on week 1, day 1. Optional 5- fluorouracil (FU) administered as a 96-hour continuous infusion (C.I.) of 1000 mg/m²/day (d) administered starting on week 1, day 1. 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 February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.	Drug: Cetuximab Drug: Cisplatin Drug: 5 - Fluorouracil
Cetuximab and Cisplatin (C)	Experimental	Cycle 1 (4 weeks, combination therapy): 100 mg/m² Cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3 and 4, day 1. Cycle 2-6 (3 weeks combination therapy): 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 250 mg/m² cetuximab admin I.V on week 1, 2, and 3, 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 February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.	Drug: Cetuximab Drug: Cisplatin Drug: 5 - Fluorouracil
Cetuximab on Cisplatin (B)	Experimental	Cycle 1: 400 mg/m² cetuximab admin I.V on week 1, day 1. 250 mg/m² cetuximab admin I.V on week 2 and 3, day 1. Cycle 2: 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1- 4. 250 mg/m² cetuximab admin I.V on week 1-3, day 1. Cycle 3 + : 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4. 250 mg/m² cetuximab admin I.V on week 1-3, 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 February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.

Interventions

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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Total Cisplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞])		Groups A and C: Cycle 1,Day 1 and Cycle 2 Day 1; Baseline (Prior to Cisplatin Infusion), 1, 1.50, 2, 3, 5, 8, 24, 72 hours (After the Start of Cisplatin Infusion).
Cetuximab Pharmacokinetics: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss)		Group B:Cycle 1,Day 15 and Cycle 2, Day 1 and Group C: Cycle 1, Day 22 and Cycle 2, Day 1: Baseline (Prior to Cetuximab Infusion),1, 2, 4, 8, 24, 72, 120, and 168 hours (After the Start of Cetuximab Infusion).
Total Cisplatin Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)		Groups A and C: Cycle 1,Day 1 and Cycle 2 Day 1; Baseline (Prior to Cisplatin Infusion), 1, 1.50, 2, 3, 5, 8, 24, 72 hours (After the Start of Cisplatin Infusion).
Cetuximab Pharmacokinetics: Maximum Observed Plasma Concentration at Steady State (Cmax,ss)		Group B:Cycle 1,Day 15 and Cycle 2, Day 1 and Group C: Cycle 1, Day 22 and Cycle 2, Day 1: Baseline (Prior to Cetuximab Infusion),1, 2, 4, 8, 24, 72, 120, and 168 hours (After the Start of Cetuximab Infusion).
Total Cisplatin Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax)		Groups A and C: Cycle 1,Day 1 and Cycle 2 Day 1; Baseline (Prior to Cisplatin Infusion), 1, 1.50, 2, 3, 5, 8, 24, 72 hours (After the Start of Cisplatin Infusion).
Cetuximab Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax)		Group B:Cycle 1,Day 15 and Cycle 2, Day 1 and Group C: Cycle 1, Day 22 and Cycle 2, Day 1: Baseline (Prior to Cetuximab Infusion),1, 2, 4, 8, 24, 72, 120, and 168 hours (After the Start of Cetuximab Infusion).

Eligibility Module

Eligibility Criteria

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, 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 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.

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	Cisplatin on Cetuximab (A)	Cycle 1: 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4. 400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3, day 1. Cycle 2 +: 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4. 250 mg/m² cetuximab admin I.V on weeks 1-3, 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 February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
FG001	Cetuximab on Cisplatin (B)	Cycle 1: 400 mg/m² cetuximab admin I.V on week 1, day 1. 250 mg/m² cetuximab admin I.V on week 2 and 3, day 1. Cycle 2: 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1- 4. 250 mg/m² cetuximab admin I.V on week 1-3, day 1. Cycle 3 + : 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4. 250 mg/m² cetuximab admin I.V on week 1-3, 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 February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
FG002	Cetuximab and Cisplatin (C)	Cycle 1 (4 weeks, combination therapy): 100 mg/m² Cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3 and 4, day 1. Cycle 2-6 (3 weeks combination therapy): 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 250 mg/m² cetuximab admin I.V on week 1, 2, and 3, 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 February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
FG003	Cetuximab and Cisplatin (D)	Cycle 1 (1 week, combination therapy): 400 milligrams per square meter (mg/m²) cetuximab administered (admin) intravenously (I.V) on week 1, day 1. 100 mg/m² cisplatin administered I.V on week 1, day 1. Optional 5- fluorouracil (FU) administered as a 96-hour continuous infusion (C.I.) of 1000 mg/m²/day (d) administered starting on week 1, day 1. 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 February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	All Participants (All Participants (Group A, B, C and D)	A:Cycle1:100mg/m² cisplatin(cs) I.V on week(w)1,day(d)1. 5-FU as a 96-hour(h) C.I. of 1000 mg/m²/d starting (st) on w 1,d 1-4. 400mg/m² cetuximab(ct) I.V on w 2,d 1.250mg/m² ct I.V on w 3,d 1.Cycle 2+100mg/m² cs I.V on w 1,d 1.5-FU as a 96-h C.I. of 1000mg/m²/d st on w 1,d 1-4.250mg/m² ct I.V on w 1-3,d 1. B:Cycle1:400mg/m² ct I.V on w 1,d 1.250mg/m² ct I.V on w 2&3,d 1.Cycle 2:100mg/m² cs I.V on w 1, d 1.5-FU as a 96-h C.I. of 1000mg/m²/d st on w 1,d 1- 4.250mg/m² ct I.V on w 1-3,d 1.Cycle 3 +:100mg/m² cs I.V on w 1,d 1.5-FU as a 96-h C.I. of 1000mg/m²/d st on w 1,d 1-4. 250mg/m² ct I.V on w 1-3,d 1. C:Cycle1:100mg/m² cs I.V on w 1, d 1. 5-FU as a 96-h C.I. of 1000mg/m²/d st on w 1,d 1.400 mg/m² ct I.V on w 2,d 1.250mg/m² ct I.V on w 3&4,d 1.Cycle2-6:100mg/m² cs I.V on w 1,d 1.5-FU as a 96-h C.I. of 1000mg/m²/d st w 1,d 1. 250mg/m² ct I.V w 1,2,&3,d 1. D:Cycle1:400mg/m² ct I.V w 1,d 1.100mg/m² cs I.V w 1,d 1.Optional 5-FU as a 96-h C.I. of 1000mg/m²/d st w 1,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 Cisplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞])

All participants who received at least one dose of study drug who were enrolled in Group A or C and had evaluable PK data. Study design by intent did not collect data from Group B or Group D.

Posted

Geometric Mean

Geometric Coefficient of Variation

micrograms*hour/milliliters (μg*h/mL)

Groups A and C: Cycle 1,Day 1 and Cycle 2 Day 1; Baseline (Prior to Cisplatin Infusion), 1, 1.50, 2, 3, 5, 8, 24, 72 hours (After the Start of Cisplatin Infusion).

ID	Title	Description
OG000	Cetuximab (A and C)	Cisplatin on Cetuximab (A) Cycle 1: 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4. 400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3, day 1. Cycle 2 +: 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4. 250 mg/m² cetuximab admin I.V on weeks 1-3, day 1. Cetuximab and Cisplatin (C) Cycle 1 (4 weeks, combination therapy): 100 mg/m² Cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3 and 4, day 1. Cycle 2-6 (3 weeks combination therapy): 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 250 mg/m² cetuximab admin I.V on week 1, 2, and 3, 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	Cisplatin on Cetuximab (A)	Cisplatin on Cetuximab (A) Cycle 1: 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4. 400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3, day 1. Cycle 2 +: 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4. 250 mg/m² cetuximab admin I.V on weeks 1-3, 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 February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.

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