Phase 1
N=59
A Study to Evaluate Corrected QT Interval and Drug-Drug Interaction of Trastuzumab on Carboplatin in the Presence of Docetaxel in Patients With HER2-Positive Metastatic or Locally Advanced Inoperable Cancer
Solid Cancers
Bottom Line
View on ClinicalTrials.gov: NCT00927589 ↗Enrolled (actual)
59
Serious AEs
44.8%
Results posted
Dec 2015
Primary outcome: Primary: Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) at Trastuzumab Steady State — -8.4 milliseconds (msec)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- carboplatin (Drug); docetaxel (Drug); trastuzumab (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Genentech, Inc.
- Primary completion
- Feb 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) at Trastuzumab Steady State |
-8.4 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Carboplatin |
51; 52 | — |
| PRIMARY Area Under the Curve From Time Zero to 6 Hours Post Infusion (AUC0-6hr) of Carboplatin |
115; 123 | — |
| PRIMARY Dose-Normalized Cmax (Cmax/D) of Carboplatin |
9; 9 | — |
| PRIMARY Geometric Mean Ratio of Cmax/D of Carboplatin |
1.02 | — |
| PRIMARY Dose-Normalized AUC0-6hr (AUC0-6hr/D) of Carboplatin |
19; 21 | — |
| PRIMARY Geometric Mean Ratio of AUC0-6hr/D of Carboplatin |
1.07 | — |
| PRIMARY Plasma Decay Half-Life (t1/2) of Carboplatin |
2; 2 | — |
| PRIMARY Maximum Observed Serum Concentration (Cmax) of Trastuzumab |
146.3; 187.1; 179.1; 181.5 | — |
| PRIMARY Minimum Observed Serum Trough Concentration (Cmin) of Trastuzumab |
0.178; 38.8; 38.7; 29.7 | — |
| SECONDARY Change From Baseline in Corrected QT Interval Using Bazett's Correction (QTcB) at Trastuzumab Steady State |
-5.9 | — |
| SECONDARY Baseline-adjusted QTcF, QTcB, PR Interval, and QRS Duration |
3.5; -9.3; -4.3; -15.6; -13.4; 3.9 | — |
| SECONDARY Baseline-adjusted Heart Rate |
0.5; 9.6; 6.2; 3.1; -0.7 | — |
| SECONDARY Number of Participants Within Each Absolute QTc Interval Category |
44; 4; 1; 0; 49; 1 | — |
| SECONDARY Number of Participants With Increase From Baseline in QTc Interval |
49; 0; 0; 50; 0; 0 | — |
| SECONDARY Number of Participants With New Abnormal U Waves on ECG |
0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With New Abnormal T Waves on ECG |
0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Abnormal Changes in PR Interval |
0; 2; 0; 1; 1; 1 | — |
| SECONDARY Number of Participants With Abnormal Changes in QRS Interval |
0; 4; 0; 0; 4; 0 | — |
| SECONDARY Population Pharmacokinetics of Trastuzumab |
— | — |
Summary
This Phase Ib, multicenter, single-arm, open-label study is designed to evaluate the effect of trastuzumab on QTcF interval and to characterize the effects of trastuzumab on carboplatin pharmacokinetics in patients with HER2-positive metastatic or locally advanced inoperable cancer.
The QT interval is a measure of time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The QTcF interval is the QT interval as calculated using Fridericia's correction; the QTcB interval is the QT interval as calculated using Bazett's correction.
Eligibility Criteria
Inclusion Criteria
- Histologic documentation of a HER2-positive solid malignancy in patients with metastatic or locally advanced inoperable disease
- Left ventricular ejection fraction (LVEF) >/= 50% by multiple-gated acquisition (MUGA) scan or two-dimensional echocardiography (ECHO) 450 ms as determined by local assessment
Data sourced from ClinicalTrials.gov (NCT00927589). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.