Trial Outcomes & Findings for Study in Advanced Solid Tumors (NCT NCT01099358)

NCT ID: NCT01099358

Last Updated: 2019-09-26

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

47 participants

Primary outcome timeframe

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).

Results posted on

2019-09-26

Participant Flow

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

\[wk 4 = wk 1 of cycle(cyc) 2\]) \& 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.

Participant milestones

Participant milestones
Measure	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.	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.	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.	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.
Overall Study STARTED	4	6	21	16
Overall Study Received at Least One Dose of Study Drug	3	6	20	15
Overall Study COMPLETED	1	5	13	12
Overall Study NOT COMPLETED	3	1	8	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study in Advanced Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants (All Participants (Group A, B, C and D) n=44 Participants 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.
Age, Continuous	56.6 years STANDARD_DEVIATION 11.29 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	34 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment Canada	16 participants n=5 Participants
Region of Enrollment United States	28 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cetuximab and Cisplatin (A and C) n=5 Participants 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.	Cetuximab (A and C) n=5 Participants 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.
Total Cisplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞])	338 microgramshour/milliliters (μgh/mL) Geometric Coefficient of Variation 26.1	324 microgramshour/milliliters (μgh/mL) Geometric Coefficient of Variation 24.5

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cetuximab and Cisplatin (A and C) n=14 Participants 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.	Cetuximab (A and C) n=14 Participants 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.
Cetuximab Pharmacokinetics: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss)	16200 microgramshour/milliliters (μgh/mL) Geometric Coefficient of Variation 22.5	15000 microgramshour/milliliters (μgh/mL) Geometric Coefficient of Variation 25.7

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Cetuximab and Cisplatin (A and C) n=5 Participants 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.	Cetuximab (A and C) n=5 Participants 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.
Total Cisplatin Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)	4.22 micrograms/milliliters(μg/mL) Geometric Coefficient of Variation 10.2	4.08 micrograms/milliliters(μg/mL) Geometric Coefficient of Variation 23.2

PRIMARY outcome

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.

Outcome measures

Outcome measures
Measure	Cetuximab and Cisplatin (A and C) n=14 Participants 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.	Cetuximab (A and C) n=14 Participants 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.
Cetuximab Pharmacokinetics: Maximum Observed Plasma Concentration at Steady State (Cmax,ss)	192 micrograms per milliliters (μg/mL) Geometric Coefficient of Variation 12.8	194 micrograms per milliliters (μg/mL) Geometric Coefficient of Variation 20.6

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Cetuximab and Cisplatin (A and C) n=5 Participants 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.	Cetuximab (A and C) n=5 Participants 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.
Total Cisplatin Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax)	1.05 Hours (h) Interval 1.0 to 1.42	1.02 Hours (h) Interval 0.97 to 1.5

PRIMARY outcome

Outcome measures

Outcome measures
Measure	Cetuximab and Cisplatin (A and C) n=14 Participants 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.	Cetuximab (A and C) n=14 Participants 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.
Cetuximab Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax)	1.99 Hours (h) Interval 1.0 to 4.18	2.00 Hours (h) Interval 1.0 to 4.05

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cetuximab and Cisplatin (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.	Cetuximab (A and C) n=11 Participants 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.
Cetuximab Pharmacokinetics: Confirmatory Serum Concentration	—	198 micrograms per milliliters (μg/mL) Geometric Coefficient of Variation 18.5

Adverse Events

Cisplatin on Cetuximab (A)

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Cetuximab on Cisplatin (B)

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Cetuximab and Cisplatin (C)

Serious events: 12 serious events

Other events: 20 other events

Deaths: 0 deaths

Cetuximab and Cisplatin (D)

Serious events: 6 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Cisplatin on Cetuximab (A) n=3 participants at risk 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.	Cetuximab on Cisplatin (B) n=6 participants at risk 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.	Cetuximab and Cisplatin (C) n=20 participants at risk 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.	Cetuximab and Cisplatin (D) n=15 participants at risk 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.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.	15.0% 3/20 • Number of events 3 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	6.7% 1/15 • Number of events 1 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukopenia	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	66.7% 2/3 • Number of events 2 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Cardiac disorders Atrial fibrillation	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 2 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	13.3% 2/15 • Number of events 2 All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Gastrointestinal disorders Dysphagia	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Gastrointestinal disorders Ileus	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	6.7% 1/15 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	66.7% 2/3 • Number of events 2 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Gastrointestinal disorders Oesophagitis	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Gastrointestinal disorders Stomatitis	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
General disorders Death	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
General disorders Fatigue	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
General disorders Mucosal inflammation	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
General disorders Pyrexia	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Immune system disorders Anaphylactic reaction	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Infections and infestations Bacteraemia	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Infections and infestations Pneumonia	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	10.0% 2/20 • Number of events 2 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Infections and infestations Sepsis	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Pubis fracture	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	6.7% 1/15 • Number of events 1 All participants who received at least one dose of study drug.
Investigations Blood creatinine increased	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	66.7% 2/3 • Number of events 3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.	10.0% 2/20 • Number of events 2 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Failure to thrive	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	33.3% 1/3 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	6.7% 1/15 • Number of events 1 All participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	6.7% 1/15 • Number of events 1 All participants who received at least one dose of study drug.
Nervous system disorders Encephalopathy	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Nervous system disorders Syncope	0.00% 0/3 All participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 All participants who received at least one dose of study drug.	15.0% 3/20 • Number of events 3 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	6.7% 1/15 • Number of events 1 All participants who received at least one dose of study drug.
Renal and urinary disorders Bladder outlet obstruction	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	6.7% 1/15 • Number of events 1 All participants who received at least one dose of study drug.
Renal and urinary disorders Renal failure	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	0.00% 0/20 All participants who received at least one dose of study drug.	6.7% 1/15 • Number of events 2 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.
Vascular disorders Thrombophlebitis	0.00% 0/3 All participants who received at least one dose of study drug.	0.00% 0/6 All participants who received at least one dose of study drug.	5.0% 1/20 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/15 All participants who received at least one dose of study drug.