A Phase 1 interventional study of Herceptin in Breast Cancer, sponsored by Hoffmann-La Roche. Completed at 3 sites in 2 countries. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-12-16.
Sponsored by Hoffmann-La Roche · Phase 1, Interventional, and Treatment
This two-part study is designed to select the subcutaneous (SC) dose of Herceptin that results in comparable exposure to intravenous (IV) Herceptin in healthy male participants and in HER2-positive female participants. The study will also assess the safety and tolerability of the SC and IV formulations. In Part 1 of the study, four cohorts will be treated with a single dose of Herceptin as follows: Cohort 1 (6 milligrams per kilogram [mg/kg] IV in healthy male participants); Cohort 2 (6 mg/kg IV in HER2-positive female participants); Cohort 3 (6 mg/kg SC in healthy male participants); Cohort 4 (10 mg/kg SC in healthy male participants). An additional cohort of healthy volunteers (Cohort 5) will be opened if both SC dose levels from Cohorts 3 and 4 result in Herceptin exposures different from the target concentration produced by a single IV dose, or if the variability in pharmacokinetic (PK) parameter values cannot be used to define the target SC dose level. In Part 2 of the study, HER2-positive female participants will receive a single dose of SC Herceptin at the dose level defined in Part 1. Participants from Part 1 are eligible to enter Part 2 provided they receive the second (Part 2) study dose of Herceptin a minimum of 22 days after their first (Part 1) dose.
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Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.
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Healthy Participants (Part 1 only)
HER2-Positive Females (Parts 1 and 2)
Exclusion Criteria:
Healthy Participants (Part 1 only)
HER2-Positive Females (Parts 1 and 2)
Healthy male participants will receive Herceptin 6 mg/kg IV on Day 1.
Drug: Herceptin
Female participants with HER2-positive breast cancer will receive Herceptin 6 mg/kg IV on Day 1.
Drug: Herceptin
Healthy male participants will receive Herceptin 6 mg/kg SC on Day 1.
Drug: Herceptin
Healthy male participants will receive Herceptin 10 mg/kg SC on Day 1.
Drug: Herceptin
Healthy male participants will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohorts 1, 2, 3, and 4.
Drug: Herceptin
Female participants with HER2-positive breast cancer will receive Herceptin SC at the dose level determined in Part 1.
Drug: Herceptin
Female participants with HER2-positive breast cancer will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohort A.
Drug: Herceptin
Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
Also known as: Trastuzumab
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUCinf) of Trastuzumab
AUCinf represents the area under the concentration-time curve of trastuzumab in serum over the time interval from 0 extrapolated to infinity. Values for AUCinf of trastuzumab were derived by non-compartmental analysis across all pharmacokinetic (PK) collections and expressed in days by micrograms per milliliter (days•μg/mL).
Time frame: Predose (0 hours) and postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)
Trough Serum Concentration on Day 22 (CDay22) of Trastuzumab
CDay22 of trastuzumab was derived from the single PK collection on Day 22 and expressed in micrograms per milliliter (μg/mL).
Time frame: Day 22
Maximum Observed Serum Concentration of Trastuzumab (Cmax)
Cmax of trastuzumab was derived across all post-dose PK collections and expressed in μg/mL.
Time frame: Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)
Time to Maximum Serum Concentration (Tmax) of Trastuzumab
Tmax of trastuzumab was based on the Cmax derived across all post-dose PK collections and expressed in hours.
Time frame: Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)
Terminal Elimination Half-Life (T1/2) of Trastuzumab
T1/2 of trastuzumab was measured as the time required for trastuzumab concentration to decrease by one-half. T1/2 was derived across all PK collections and expressed in hours.
Time frame: Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)
| Milestone | Part 1: Cohort 1 | Part 1: Cohort 2 | Part 1: Cohort 3 | Part 1: Cohort 4 | Part 1: Cohort 5 | Part 2: Cohort A | Part 2: Cohort B |
|---|---|---|---|---|---|---|---|
| Started | 6 | 6 | 6 | 6 | 6 | 20 | 20 |
| Completed | 6 | 6 | 5 | 5 | 6 | 20 | 20 |
| Not completed | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
AUCinf represents the area under the concentration-time curve of trastuzumab in serum over the time interval from 0 extrapolated to infinity. Values for AUCinf of trastuzumab were derived by non-compartmental analysis across all pharmacokinetic (PK) collections and expressed in days by micrograms per milliliter (days•μg/mL).
| days•μg/mL | Part 1: Cohort 1 | Part 1: Cohort 2 | Part 1: Cohort 3 | Part 1: Cohort 4 | Part 1: Cohort 5 | Part 2: Cohort A | Part 2: Cohort B |
|---|---|---|---|---|---|---|---|
| Area Under the Concentration-Time Curve Extrapolated to Infinity (AUCinf) of Trastuzumab | 1610 ± 303 | 1800 ± 250 | 1350 ± 320 | 2500 ± 515 | 1960 ± 244 | 2090 ± 638 | 3550 ± 982 |
CDay22 of trastuzumab was derived from the single PK collection on Day 22 and expressed in micrograms per milliliter (μg/mL).
| μg/mL | Part 1: Cohort 1 | Part 1: Cohort 2 | Part 1: Cohort 3 | Part 1: Cohort 4 | Part 1: Cohort 5 | Part 2: Cohort A | Part 2: Cohort B |
|---|---|---|---|---|---|---|---|
| Trough Serum Concentration on Day 22 (CDay22) of Trastuzumab | 25.6 ± 12.1 | 27.5 ± 7.5 | 31.6 ± 12.0 | 51.4 ± 15.8 | 39.4 ± 5.5 | 37.8 ± 10.4 | 60.8 ± 22.0 |
Cmax of trastuzumab was derived across all post-dose PK collections and expressed in μg/mL.
| μg/mL | Part 1: Cohort 1 | Part 1: Cohort 2 | Part 1: Cohort 3 | Part 1: Cohort 4 | Part 1: Cohort 5 | Part 2: Cohort A | Part 2: Cohort B |
|---|---|---|---|---|---|---|---|
| Maximum Observed Serum Concentration of Trastuzumab (Cmax) | 150 ± 14.4 | 185 ± 42.9 | 66.8 ± 11.4 | 102 ± 17.2 | 82.0 ± 11.3 | 88.4 ± 33.3 | 151 ± 58.6 |
Tmax of trastuzumab was based on the Cmax derived across all post-dose PK collections and expressed in hours.
| hours | Part 1: Cohort 1 | Part 1: Cohort 2 | Part 1: Cohort 3 | Part 1: Cohort 4 | Part 1: Cohort 5 | Part 2: Cohort A | Part 2: Cohort B |
|---|---|---|---|---|---|---|---|
| Time to Maximum Serum Concentration (Tmax) of Trastuzumab | 1.65 (1.6 to 24.0) | 3.00 (1.55 to 24.0) | 156.00 (95.95 to 216.10) | 132.12 (96.00 to 216.00) | 96.00 (96.00 to 215.98) | 97.13 (47.93 to 216.60) | 96.05 (24.53 to 241.40) |
T1/2 of trastuzumab was measured as the time required for trastuzumab concentration to decrease by one-half. T1/2 was derived across all PK collections and expressed in hours.
| hours | Part 1: Cohort 1 | Part 1: Cohort 2 | Part 1: Cohort 3 | Part 1: Cohort 4 | Part 1: Cohort 5 | Part 2: Cohort A | Part 2: Cohort B |
|---|---|---|---|---|---|---|---|
| Terminal Elimination Half-Life (T1/2) of Trastuzumab | 254 ± 32.2 | 244 ± 69.2 | 227 ± 55.9 | 240 ± 34.4 | 236 ± 43.9 | 241 ± 48.1 | 270 ± 80.1 |
Collected over From Baseline up to 5 months post-dose (up to 5 months overall). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1: Cohort 1 | — | 0/6 (0%) | 5/6 (83.3%) |
| Part 1: Cohort 2 | — | 0/6 (0%) | 6/6 (100%) |
| Part 1: Cohort 3 | — | 0/6 (0%) | 5/6 (83.3%) |
| Part 1: Cohort 4 | — | 0/6 (0%) | 5/6 (83.3%) |
| Part 1: Cohort 5 | — | 0/6 (0%) | 6/6 (100%) |
| Part 2: Cohort A | — | 0/20 (0%) | 19/20 (95%) |
| Part 2: Cohort B | — | 0/20 (0%) | 20/20 (100%) |
| Event | Part 1: Cohort 1 | Part 1: Cohort 2 | Part 1: Cohort 3 | Part 1: Cohort 4 | Part 1: Cohort 5 | Part 2: Cohort A | Part 2: Cohort B |
|---|---|---|---|---|---|---|---|
| HeadacheNervous system disorders | 3/6 | 2/6 | 2/6 | 0/6 | 2/6 | 12/20 | 14/20 |
| Injection site discolourationGeneral disorders | 0/6 | 0/6 | 2/6 | 0/6 | 0/6 | 3/20 | 0/20 |
| Infusion related reactionGeneral disorders | 2/6 | 0/6 | 0/6 | 0/6 | 0/6 | 0/20 | 0/20 |
| Upper respiratory tract InfectionInfections and infestations | 0/6 | 0/6 | 1/6 | 2/6 | 1/6 | 4/20 | 5/20 |
| Musculoskeletal painMusculoskeletal and connective tissue disorders | 2/6 | 1/6 | 0/6 | 0/6 | 0/6 | 0/20 | 1/20 |
| DiarrhoeaGastrointestinal disorders | 2/6 | 0/6 | 0/6 | 0/6 | 0/6 | 6/20 | 2/20 |
| Abdominal painGastrointestinal disorders | 2/6 | 0/6 | 0/6 | 0/6 | 0/6 | 0/20 | 0/20 |
| AcneSkin and subcutaneous tissue disorders | 0/6 | 2/6 | 0/6 | 0/6 | 0/6 | 0/20 | 0/20 |
| Injection site erythemaGeneral disorders | 0/6 | 0/6 | 1/6 | 0/6 | 0/6 | 4/20 | 2/20 |
| LethargyNervous system disorders | 1/6 | 0/6 | 0/6 | 0/6 | 0/6 | 4/20 | 2/20 |
Safety Population: All participants who received at least one dose of study medication, whether prematurely withdrawn from the study or not. The "Total" column (n=70) includes 4 female participants who were counted twice as they were treated in both Cohort 2 and Cohort A.
| Age, Continuous(years) | Part 1: Cohort 1 | Part 1: Cohort 2 | Part 1: Cohort 3 | Part 1: Cohort 4 | Part 1: Cohort 5 | Part 2: Cohort A | Part 2: Cohort B | Total |
|---|---|---|---|---|---|---|---|---|
| Mean | 22.7 ± 2.58 | 46.2 ± 5.19 | 25.7 ± 9.29 | 23.0 ± 6.16 | 22.0 ± 4.34 | 50.7 ± 7.21 | 51.6 ± 9.04 | 41.2 ± 14.85 |
| Gender(Participants) | Part 1: Cohort 1 | Part 1: Cohort 2 | Part 1: Cohort 3 | Part 1: Cohort 4 | Part 1: Cohort 5 | Part 2: Cohort A | Part 2: Cohort B | Total |
|---|---|---|---|---|---|---|---|---|
| Female | 0 | 6 | 0 | 0 | 0 | 20 | 20 | 46 |
| Male | 6 | 0 | 6 | 6 | 6 | 0 | 0 | 24 |
This study is completed, as verified in Oct 2016. You cannot join it, but the record below documents what was studied.
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Hoffmann-La Roche