Solid Tumor
Conditions
Keywords
Cancer of Head, Cancer of Head and Neck, Cancer of Neck, Cancer of the Head, Cancer of the Head and Neck, Cancer of the 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 cisplatin \[pharmacokinetic (PK) analysis\] * To see if any drug interactions occur between cetuximab and cisplatin.
Interventions
DRUGCetuximab
Administered Intravenously
DRUGCisplatin
Administered Intravenously
DRUG5 - Fluorouracil
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 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.
Design outcomes
Primary
| Measure | 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). |
| Cetuximab Pharmacokinetics: Confirmatory Serum Concentration | Group D:Cycle 1, Day 1: Prior to Cisplatin Infusion. |
Countries
Canada, United States
Participant flow
Recruitment details
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(cet) and cisplatin(D) arm only. Group(Grp)A (cisplatin \[cis\]) completed 3 infusions(inf) of cet (Weeks(wk) 2,3, & 4
Pre-assignment details
\[wk 4 = wk 1 of cycle(cyc) 2\]) & 2 inf of cis(wk 1 & 4) first 4 wks.Grp B (cet) completed 4 inf of cet (wk 1-4) & 1 inf of cis(wk 4) first 4 wks. Grp C(cis and cet) completed 4 inf of cet(wk 2,3,4, & 5) & 2 inf of cis(wk 1 & 5) first 5 wk. Grp D(cis) completed 1 inf of cet(cyc 1) & 1 inf of cis(wk 1 of cyc 1) and without deviation.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 44 |
| Total | 44 |
Baseline characteristics
| Characteristic | All Participants (All Participants (Group A, B, C and D) |
|---|---|
| Age, Continuous | 56.6 years STANDARD_DEVIATION 11.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 5 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 | 34 Participants |
| Region of Enrollment Canada | 16 participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 25 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 | 3 / 3 | 6 / 6 | 20 / 20 | 15 / 15 |
| serious Total, serious adverse events | 3 / 3 | 3 / 6 | 12 / 20 | 6 / 15 |
Outcome results
Primary
Cetuximab Pharmacokinetics: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss)
Time frame: 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).
Population: All participants who received at least one dose of study drug who were enrolled in Group B or C and had evaluable PK data. Study design by intent did not collect data from Group A or Group D.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cetuximab (A and C) | Cetuximab Pharmacokinetics: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss) | 15000 micrograms*hour/milliliters (μg*h/mL) | Geometric Coefficient of Variation 25.7 |
| Cetuximab and Cisplatin (A and C) | Cetuximab Pharmacokinetics: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss) | 16200 micrograms*hour/milliliters (μg*h/mL) | Geometric Coefficient of Variation 22.5 |
Primary
Cetuximab Pharmacokinetics: Confirmatory Serum Concentration
Time frame: Group D:Cycle 1, Day 1: Prior to Cisplatin Infusion.
Population: All participants who received at least one dose of study drug who were enrolled in Group D and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cetuximab (A and C) | Cetuximab Pharmacokinetics: Confirmatory Serum Concentration | 198 micrograms per milliliters (μg/mL) | Geometric Coefficient of Variation 18.5 |
Primary
Cetuximab Pharmacokinetics: Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
Time frame: 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).
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 Group A or Group D.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cetuximab (A and C) | Cetuximab Pharmacokinetics: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 194 micrograms per milliliters (μg/mL) | Geometric Coefficient of Variation 20.6 |
| Cetuximab and Cisplatin (A and C) | Cetuximab Pharmacokinetics: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 192 micrograms per milliliters (μg/mL) | Geometric Coefficient of Variation 12.8 |
Primary
Cetuximab Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax)
Time frame: 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).
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 Group A or Group D.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab (A and C) | Cetuximab Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax) | 2.00 Hours (h) |
| Cetuximab and Cisplatin (A and C) | Cetuximab Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax) | 1.99 Hours (h) |
Primary
Total Cisplatin Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)
Time frame: 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).
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cetuximab (A and C) | Total Cisplatin Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 4.08 micrograms/milliliters(μg/mL) | Geometric Coefficient of Variation 23.2 |
| Cetuximab and Cisplatin (A and C) | Total Cisplatin Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 4.22 micrograms/milliliters(μg/mL) | Geometric Coefficient of Variation 10.2 |
Primary
Total Cisplatin Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax)
Time frame: 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).
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab (A and C) | Total Cisplatin Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax) | 1.02 Hours (h) |
| Cetuximab and Cisplatin (A and C) | Total Cisplatin Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax) | 1.05 Hours (h) |
Primary
Total Cisplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞])
Time frame: 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).
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cetuximab (A and C) | Total Cisplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) | 324 micrograms*hour/milliliters (μg*h/mL) | Geometric Coefficient of Variation 24.5 |
| Cetuximab and Cisplatin (A and C) | Total Cisplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) | 338 micrograms*hour/milliliters (μg*h/mL) | Geometric Coefficient of Variation 26.1 |