A Study in Advanced Solid Tumors
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01063075
Collaborator
(none)
34
8
4
64
4.3
0.1
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
34 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Phase 2 Study to Evaluate the Pharmacokinetics and Drug-Drug Interaction of Cetuximab and Carboplatin in Patients With Advanced Solid Tumors
Study Start Date
:
Jun 1, 2010
Actual Primary Completion Date
:
May 1, 2015
Actual Study Completion Date
:
Oct 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. 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
Administered Intravenously
Drug: Carboplatin
Administered Intravenously
Drug: 5 - FU
Administered Intravenously
|
| Experimental: 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. 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
Administered Intravenously
Drug: Carboplatin
Administered Intravenously
Drug: 5 - FU
Administered Intravenously
|
| Experimental: 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. 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
Administered Intravenously
Drug: Carboplatin
Administered Intravenously
Drug: 5 - FU
Administered Intravenously
|
| Experimental: 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. 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. |
Drug: Cetuximab
Administered Intravenously
Drug: Carboplatin
Administered Intravenously
Drug: 5 - FU
Administered Intravenously
|
Outcome Measures
Primary Outcome Measures
- 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]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Highlands Oncology Group | Fayetteville | Arkansas | United States | 72703 |
| 2 | University of Kansas Medical Center | Fairway | Kansas | United States | 66205 |
| 3 | Portland VA Medical Center | Portland | Oregon | United States | 91239 |
| 4 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
| 5 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
| 6 | University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 7 | 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. | London | Ontario | Canada | N6A 4L6 |
| 8 | 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 | H3G 1A4 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: 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 Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01063075
Other Study ID Numbers:
- 13420
- I4E-MC-JXBB
First Posted:
Feb 5, 2010
Last Update Posted:
Sep 26, 2019
Last Verified:
Sep 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Carboplatin and Cetuximab (A) | Cetuximab and Carboplatin (B) | Cetuximab and Carboplatin (C) | Cetuximab and Carboplatin (D) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Period Title: Overall Study | ||||
| STARTED | 2 | 3 | 14 | 15 |
| COMPLETED | 1 | 1 | 9 | 14 |
| NOT COMPLETED | 1 | 2 | 5 | 1 |
Baseline Characteristics
| Arm/Group Title | All Participants (Group A, B, C and D) |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 34 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
58.20
(12.88)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
8
23.5%
|
| Male |
26
76.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
34
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
2
5.9%
|
| White |
31
91.2%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
1
2.9%
|
| Region of Enrollment (participants) [Number] | |
| Canada |
10
29.4%
|
| United States |
24
70.6%
|
Outcome Measures
| Title | Total Carboplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) |
|---|---|
| Description | |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Cetuximab and Carboplatin (D) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 13 |
| Geometric Mean (Geometric Coefficient of Variation) [micrograms*hour/milliliters (μg•h/mL)] |
129
(14.8)
|
| Title | Cetuximab PK: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss) |
|---|---|
| Description | |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Cetuximab (B and C) | Cetuximab and Carboplatin (B and C) |
|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. |
| Measure Participants | 5 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [micrograms*hour/milliliters (μg•h/mL)] |
17200
(15.8)
|
16700
(18.5)
|
| Title | Total Carboplatin PK: Maximum Observed Plasma Concentration (Cmax) |
|---|---|
| Description | |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Cetuximab and Carboplatin (D) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 13 |
| Geometric Mean (Geometric Coefficient of Variation) [micrograms per milliliters (μg/mL)] |
11.5
(15.8)
|
| Title | Cetuximab PK: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) |
|---|---|
| Description | |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Cetuximab (B and C) | Cetuximab and Carboplatin (B and C) |
|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. |
| Measure Participants | 5 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [micrograms per milliliters (μg/mL)] |
199
(10.3)
|
199
(10.8)
|
| Title | Total Carboplatin PK: Time of Maximum Observed Plasma Concentration (Tmax) |
|---|---|
| Description | |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Cetuximab and Carboplatin (D) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 13 |
| Median (Full Range) [Hour (h)] |
1.12
|
| Title | Cetuximab PK: Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) |
|---|---|
| Description | |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Cetuximab (B and C) | Cetuximab and Carboplatin (B and C) |
|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. |
| Measure Participants | 5 | 5 |
| Median (Full Range) [Hour (h)] |
1.15
|
3.17
|
| Title | Cetuximab PK: Confirmatory Serum Concentration |
|---|---|
| Description | |
| Time Frame | Group D: Prior to Carboplatin Infusion, Cycle 1, Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Cetuximab (D) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 14 |
| Geometric Mean (Geometric Coefficient of Variation) [micrograms per milliliters (µg/mL)] |
195
(16.5)
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Carboplatin and Cetuximab (A) | Carboplatin and Cetuximab (B) | Carboplatin and Cetuximab (C) | Carboplatin and Cetuximab (D) | ||||
| Arm/Group Description | 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. | 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. | 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, day1. 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. | Group D: Cycle 1 (1 week, combination therapy): 400 milligrams per square meter (mg/m ²) cetuximab administered intravenously (I.V) on day 1. Carboplatin area under the curve (AUC=5) administered I.V on day 1. Optional 5- fluorouracil (FU) administered as a 96-hour continuous infusion (C.I.) of 1000 mg/ m ²/day administered starting on day 1. | ||||
All Cause Mortality |
||||||||
| Carboplatin and Cetuximab (A) | Carboplatin and Cetuximab (B) | Carboplatin and Cetuximab (C) | Carboplatin and Cetuximab (D) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Carboplatin and Cetuximab (A) | Carboplatin and Cetuximab (B) | Carboplatin and Cetuximab (C) | Carboplatin and Cetuximab (D) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/2 (50%) | 1/3 (33.3%) | 5/14 (35.7%) | 10/15 (66.7%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Leukopenia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Neutropenia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Thrombocytopenia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Cardiac disorders | ||||||||
| Acute myocardial infarction | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Atrial fibrillation | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 |
| Cardio-respiratory arrest | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Ear and labyrinth disorders | ||||||||
| Deafness | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Colitis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| General disorders | ||||||||
| Non-cardiac chest pain | 1/2 (50%) | 1 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| Pyrexia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Hepatobiliary disorders | ||||||||
| Cholangitis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Infections and infestations | ||||||||
| Pneumocystis jirovecii pneumonia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Pneumonia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Sepsis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Urinary tract infection | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 2/15 (13.3%) | 2 |
| Injury, poisoning and procedural complications | ||||||||
| Foreign body | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Hypokalaemia | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Pain in extremity | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Cancer pain | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Nervous system disorders | ||||||||
| Cerebrovascular accident | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Generalised tonic-clonic seizure | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Lethargy | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| Seizure | 1/2 (50%) | 1 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Haematuria | 1/2 (50%) | 1 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Obstructive uropathy | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnoea | 1/2 (50%) | 1 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| Laryngeal haematoma | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Laryngeal oedema | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Pleural effusion | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Respiratory failure | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||
| Carboplatin and Cetuximab (A) | Carboplatin and Cetuximab (B) | Carboplatin and Cetuximab (C) | Carboplatin and Cetuximab (D) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/2 (100%) | 2/3 (66.7%) | 14/14 (100%) | 15/15 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 1/2 (50%) | 2 | 0/3 (0%) | 0 | 4/14 (28.6%) | 6 | 6/15 (40%) | 15 |
| Leukopenia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 2/14 (14.3%) | 2 | 0/15 (0%) | 0 |
| Lymphadenopathy | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 |
| Neutropenia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 2/14 (14.3%) | 8 | 2/15 (13.3%) | 2 |
| Thrombocytopenia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 3/14 (21.4%) | 9 | 3/15 (20%) | 5 |
| Cardiac disorders | ||||||||
| Angina pectoris | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Arrhythmia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Atrial fibrillation | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Sinus tachycardia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Supraventricular tachycardia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Tachycardia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 2/15 (13.3%) | 2 |
| Ear and labyrinth disorders | ||||||||
| Deafness | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Hyperacusis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Tinnitus | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Eye disorders | ||||||||
| Eye discharge | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Eye pain | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Ocular hyperaemia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Photophobia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 2/15 (13.3%) | 2 |
| Retinal haemorrhage | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Vision blurred | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Visual impairment | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Abdominal distension | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Abdominal pain | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 2/14 (14.3%) | 3 | 3/15 (20%) | 3 |
| Anal haemorrhage | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Ascites | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Colitis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Constipation | 1/2 (50%) | 1 | 1/3 (33.3%) | 3 | 5/14 (35.7%) | 5 | 2/15 (13.3%) | 2 |
| Diarrhoea | 1/2 (50%) | 1 | 1/3 (33.3%) | 1 | 8/14 (57.1%) | 14 | 3/15 (20%) | 3 |
| Dry mouth | 1/2 (50%) | 1 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Dysphagia | 1/2 (50%) | 1 | 0/3 (0%) | 0 | 7/14 (50%) | 9 | 0/15 (0%) | 0 |
| Faeces soft | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 2/14 (14.3%) | 2 | 1/15 (6.7%) | 1 |
| Glossodynia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 2 | 0/15 (0%) | 0 |
| Haemorrhoids | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 |
| Lip swelling | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 2 | 0/15 (0%) | 0 |
| Nausea | 0/2 (0%) | 0 | 1/3 (33.3%) | 4 | 11/14 (78.6%) | 25 | 8/15 (53.3%) | 10 |
| Salivary gland disorder | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Stomatitis | 0/2 (0%) | 0 | 2/3 (66.7%) | 2 | 5/14 (35.7%) | 8 | 4/15 (26.7%) | 5 |
| Tongue haemorrhage | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Vomiting | 0/2 (0%) | 0 | 2/3 (66.7%) | 11 | 6/14 (42.9%) | 14 | 5/15 (33.3%) | 5 |
| General disorders | ||||||||
| Asthenia | 1/2 (50%) | 1 | 0/3 (0%) | 0 | 4/14 (28.6%) | 6 | 1/15 (6.7%) | 1 |
| Catheter site bruise | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Catheter site pain | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Catheter site rash | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Chest pain | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Decreased activity | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Face oedema | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Fatigue | 1/2 (50%) | 1 | 2/3 (66.7%) | 9 | 7/14 (50%) | 10 | 9/15 (60%) | 11 |
| Infusion site rash | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| Local swelling | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Malaise | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Mucosal inflammation | 1/2 (50%) | 1 | 1/3 (33.3%) | 1 | 7/14 (50%) | 23 | 3/15 (20%) | 4 |
| Oedema peripheral | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 3/14 (21.4%) | 4 | 2/15 (13.3%) | 2 |
| Pain | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Peripheral swelling | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Pyrexia | 0/2 (0%) | 0 | 1/3 (33.3%) | 2 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 |
| Hepatobiliary disorders | ||||||||
| Hepatic failure | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Hyperbilirubinaemia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Infections and infestations | ||||||||
| Bacteraemia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Candida infection | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 2/14 (14.3%) | 2 | 0/15 (0%) | 0 |
| Conjunctivitis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Folliculitis | 0/2 (0%) | 0 | 1/3 (33.3%) | 2 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| Infection | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| Nail infection | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| Opportunistic infection | 0/2 (0%) | 0 | 1/3 (33.3%) | 3 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| Oral candidiasis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 2/15 (13.3%) | 3 |
| Pharyngitis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Rash pustular | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 |
| Skin infection | 0/2 (0%) | 0 | 1/3 (33.3%) | 3 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| Upper respiratory tract infection | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Urinary tract infection | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Wound infection | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Fall | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Feeding tube complication | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Human bite | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Infusion related reaction | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Radiation skin injury | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Wound complication | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 2 | 0/15 (0%) | 0 |
| Investigations | ||||||||
| Alanine aminotransferase decreased | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Alanine aminotransferase increased | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 2/15 (13.3%) | 2 |
| Aspartate aminotransferase increased | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Blood alkaline phosphatase increased | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 2 | 1/15 (6.7%) | 1 |
| Blood bilirubin increased | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Blood creatinine increased | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 2/15 (13.3%) | 2 |
| Blood lactate dehydrogenase increased | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Breath sounds abnormal | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Electrocardiogram qt prolonged | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Haemoglobin decreased | 0/2 (0%) | 0 | 2/3 (66.7%) | 6 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| International normalised ratio increased | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Monocyte count increased | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Neutrophil count decreased | 0/2 (0%) | 0 | 1/3 (33.3%) | 2 | 2/14 (14.3%) | 2 | 1/15 (6.7%) | 3 |
| Platelet count decreased | 1/2 (50%) | 4 | 1/3 (33.3%) | 3 | 3/14 (21.4%) | 4 | 6/15 (40%) | 20 |
| Weight decreased | 0/2 (0%) | 0 | 1/3 (33.3%) | 2 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 |
| White blood cell count decreased | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 5/14 (35.7%) | 11 | 5/15 (33.3%) | 6 |
| Dehydration | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 4/14 (28.6%) | 7 | 2/15 (13.3%) | 2 |
| Hyperglycaemia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Hyperkalaemia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Hyperphosphataemia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Hypoalbuminaemia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 |
| Hypoglycaemia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 2 |
| Hypokalaemia | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 3/14 (21.4%) | 3 | 9/15 (60%) | 13 |
| Hypomagnesaemia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 4/14 (28.6%) | 9 | 6/15 (40%) | 11 |
| Hyponatraemia | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 2/14 (14.3%) | 3 | 3/15 (20%) | 7 |
| Lactic acidosis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Magnesium deficiency | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Vitamin d deficiency | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 2/14 (14.3%) | 2 | 1/15 (6.7%) | 2 |
| Muscle spasms | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Muscular weakness | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 2 |
| Musculoskeletal chest pain | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Musculoskeletal pain | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Myalgia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Neck pain | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 2/14 (14.3%) | 2 | 0/15 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Tumour pain | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 2 | 0/15 (0%) | 0 |
| Nervous system disorders | ||||||||
| Ataxia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 2 |
| Disturbance in attention | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Dizziness | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 2/14 (14.3%) | 2 | 0/15 (0%) | 0 |
| Dysgeusia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 3/14 (21.4%) | 5 | 1/15 (6.7%) | 1 |
| Headache | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 2/14 (14.3%) | 3 | 3/15 (20%) | 4 |
| Memory impairment | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Muscle tone disorder | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Neuralgia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Neuropathy peripheral | 1/2 (50%) | 1 | 0/3 (0%) | 0 | 2/14 (14.3%) | 2 | 0/15 (0%) | 0 |
| Peripheral motor neuropathy | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 2 |
| Reflexes abnormal | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Syncope | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Tremor | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Trigeminal neuralgia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 3 | 0/15 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Anxiety | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 2/15 (13.3%) | 2 |
| Depression | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 2/14 (14.3%) | 3 | 0/15 (0%) | 0 |
| Insomnia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 4/14 (28.6%) | 5 | 1/15 (6.7%) | 1 |
| Mood altered | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Dysuria | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Haematuria | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Nocturia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 |
| Polyuria | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Proteinuria | 0/2 (0%) | 0 | 1/3 (33.3%) | 2 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Menorrhagia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 |
| Pelvic pain | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Vaginal discharge | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 |
| Vulvovaginal pain | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 2/14 (14.3%) | 5 | 2/15 (13.3%) | 2 |
| Dyspnoea | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 4/15 (26.7%) | 4 |
| Epistaxis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 2/14 (14.3%) | 2 | 2/15 (13.3%) | 2 |
| Hiccups | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 2 | 0/15 (0%) | 0 |
| Oropharyngeal discomfort | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Oropharyngeal pain | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 4/14 (28.6%) | 4 | 1/15 (6.7%) | 1 |
| Pleural effusion | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Productive cough | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 2 | 1/15 (6.7%) | 1 |
| Pulmonary embolism | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Rhinitis allergic | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Rhinorrhoea | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Tachypnoea | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Wheezing | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 5/14 (35.7%) | 5 | 0/15 (0%) | 0 |
| Dermatitis acneiform | 1/2 (50%) | 1 | 0/3 (0%) | 0 | 7/14 (50%) | 15 | 9/15 (60%) | 14 |
| Dry skin | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 3/14 (21.4%) | 3 | 0/15 (0%) | 0 |
| Exfoliative rash | 0/2 (0%) | 0 | 1/3 (33.3%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 |
| Hirsutism | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/4 (25%) | 1 |
| Hyperhidrosis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Nail discolouration | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Nail disorder | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Onychoclasis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Palmar-plantar erythrodysaesthesia syndrome | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 4/14 (28.6%) | 11 | 1/15 (6.7%) | 1 |
| Petechiae | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Pruritus | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Purpura | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Rash | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 5/14 (35.7%) | 6 | 0/15 (0%) | 0 |
| Rash erythematous | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Skin hyperpigmentation | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 |
| Skin hypopigmentation | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Swelling face | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Urticaria | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Vascular disorders | ||||||||
| Deep vein thrombosis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 |
| Flushing | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
| Hypotension | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 3 | 0/15 (0%) | 0 |
| Jugular vein thrombosis | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 2/14 (14.3%) | 2 | 0/15 (0%) | 0 |
| Orthostatic hypotension | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 |
| Pallor | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 |
Limitations/Caveats
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.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01063075
Other Study ID Numbers:
- 13420
- I4E-MC-JXBB
First Posted:
Feb 5, 2010
Last Update Posted:
Sep 26, 2019
Last Verified:
Sep 1, 2019