Solid Tumor
Conditions
Keywords
Cancer of Head, Cancer of Head and Neck, Cancer of Neck, Head and Neck Cancer, Head Cancer, Head Neoplasms, Head, Neck Neoplasms, Neck Cancer, Neck Neoplasms, Solid Neoplasm, Carcinoma, Sarcoma
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.
Interventions
DRUGCetuximab
Administered Intravenously
DRUGCarboplatin
Administered Intravenously
DRUG5 - FU
Administered Intravenously
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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) |
| Cetuximab PK: Confirmatory Serum Concentration | Group D: Prior to Carboplatin Infusion, Cycle 1, Day 1 |
Countries
Canada, United States
Participant flow
Pre-assignment details
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 were placed into Group D arm only.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | All Participants (Group A, B, C and D) |
|---|---|
| Age, Continuous | 58.20 years STANDARD_DEVIATION 12.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Region of Enrollment Canada | 10 participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 2 / 3 | 14 / 14 | 15 / 15 |
| serious Total, serious adverse events | 1 / 2 | 1 / 3 | 5 / 14 | 10 / 15 |
Outcome results
Primary
Cetuximab PK: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss)
Time frame: (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)
Population: All participants who received at least one dose of study drug who were enrolled in Group B and C and had evaluable PK data. Study design by intent did not collect data from Groups D and A.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cetuximab and Carboplatin (D) | Cetuximab PK: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss) | 17200 micrograms*hour/milliliters (μg•h/mL) | Geometric Coefficient of Variation 15.8 |
| Cetuximab and Carboplatin (B and C) | Cetuximab PK: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss) | 16700 micrograms*hour/milliliters (μg•h/mL) | Geometric Coefficient of Variation 18.5 |
Primary
Cetuximab PK: Confirmatory Serum Concentration
Time frame: Group D: Prior to Carboplatin Infusion, Cycle 1, Day 1
Population: All participants who received at least one dose of study drug who were enrolled in Group D and had evaluable PK data. Study design by intent did not collect data from Groups A, B, and C.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cetuximab and Carboplatin (D) | Cetuximab PK: Confirmatory Serum Concentration | 195 micrograms per milliliters (µg/mL) | Geometric Coefficient of Variation 16.5 |
Primary
Cetuximab PK: Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
Time frame: (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)
Population: All participants who received at least one dose of study drug who were enrolled in Group B and C and had evaluable PK data. Study design by intent did not collect data from Groups D and A.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cetuximab and Carboplatin (D) | Cetuximab PK: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 199 micrograms per milliliters (μg/mL) | Geometric Coefficient of Variation 10.3 |
| Cetuximab and Carboplatin (B and C) | Cetuximab PK: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 199 micrograms per milliliters (μg/mL) | Geometric Coefficient of Variation 10.8 |
Primary
Cetuximab PK: Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss)
Time frame: (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)
Population: All participants who received at least one dose of study drug who were enrolled in Group B and C and had evaluable PK data. Study design by intent did not collect data from Groups D and A.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab and Carboplatin (D) | Cetuximab PK: Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) | 1.15 Hour (h) |
| Cetuximab and Carboplatin (B and C) | Cetuximab PK: Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) | 3.17 Hour (h) |
Primary
Total Carboplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞])
Time frame: 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)
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cetuximab and Carboplatin (D) | Total Carboplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) | 129 micrograms*hour/milliliters (μg•h/mL) | Geometric Coefficient of Variation 14.8 |
Primary
Total Carboplatin PK: Maximum Observed Plasma Concentration (Cmax)
Time frame: 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)
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cetuximab and Carboplatin (D) | Total Carboplatin PK: Maximum Observed Plasma Concentration (Cmax) | 11.5 micrograms per milliliters (μg/mL) | Geometric Coefficient of Variation 15.8 |
Primary
Total Carboplatin PK: Time of Maximum Observed Plasma Concentration (Tmax)
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab and Carboplatin (D) | Total Carboplatin PK: Time of Maximum Observed Plasma Concentration (Tmax) | 1.12 Hour (h) |