Clinical trial NCT00927589: 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
Official title: A Phase 1b, Single-arm, Open-label Clinical Trial to Evaluate Corrected QT Interval and Drug-drug Interaction of Trastuzumab on Carboplatin in the Presence of Docetaxel in Patients With Metastatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Cancers
Keywords: HER2+ Metastatic Cancer
HER2+ Locally Advanced Inoperable Cancer
HER2+ Solid Malignancy
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2009-06-25
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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) \</= 42 days prior to Cycle 1, Day 1

Exclusion Criteria:

* History of trastuzumab treatment \</= 100 days prior to Cycle 1, Day 1
* Pretreatment QTcF interval \> 450 ms as determined by local assessment

Primary outcomes:
measure: Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) at Trastuzumab Steady State
timeFrame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1
measure: Maximum Observed Plasma Concentration (Cmax) of Carboplatin
timeFrame: 0 to 5 minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)
measure: Area Under the Curve From Time Zero to 6 Hours Post Infusion (AUC0-6hr) of Carboplatin
timeFrame: 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)
measure: Dose-Normalized Cmax (Cmax/D) of Carboplatin
timeFrame: 0 to 5 minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)
measure: Geometric Mean Ratio of Cmax/D of Carboplatin
timeFrame: 0 to 5 minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)
measure: Dose-Normalized AUC0-6hr (AUC0-6hr/D) of Carboplatin
timeFrame: 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)
measure: Geometric Mean Ratio of AUC0-6hr/D of Carboplatin
timeFrame: 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)
measure: Plasma Decay Half-Life (t1/2) of Carboplatin
timeFrame: 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)
measure: Maximum Observed Serum Concentration (Cmax) of Trastuzumab
timeFrame: 30 (±15) minutes after the end of the infusion on Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 3 Day 1
measure: Minimum Observed Serum Trough Concentration (Cmin) of Trastuzumab
timeFrame: 15 (±15) minutes prior to the start of the trastuzumab infusion on Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 3 Day 1
Secondary outcomes:
measure: Change From Baseline in Corrected QT Interval Using Bazett's Correction (QTcB) at Trastuzumab Steady State
timeFrame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1
measure: Baseline-adjusted QTcF, QTcB, PR Interval, and QRS Duration
timeFrame: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)
measure: Baseline-adjusted Heart Rate
timeFrame: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)
measure: Number of Participants Within Each Absolute QTc Interval Category
timeFrame: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)
measure: Number of Participants With Increase From Baseline in QTc Interval
timeFrame: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)
measure: Number of Participants With New Abnormal U Waves on ECG
timeFrame: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)
measure: Number of Participants With New Abnormal T Waves on ECG
timeFrame: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)
measure: Number of Participants With Abnormal Changes in PR Interval
timeFrame: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)
measure: Number of Participants With Abnormal Changes in QRS Interval
timeFrame: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)
measure: Population Pharmacokinetics of Trastuzumab
timeFrame: 15 (±15) minutes prior to the start of the trastuzumab infusion, and 30 (±15) minutes after the end of the infusion on Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 3 Day 1
Other outcomes:
Locations:
city: Scottsdale
country: United States
state: Arizona
city: Beverly Hills
country: United States
state: California
city: La Jolla
country: United States
state: California
city: San Diego
country: United States
state: California
city: Santa Rosa
country: United States
state: California
city: Whittier
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Wichita
country: United States
state: Kansas
city: Billings
country: United States
state: Montana
city: Farmington
country: United States
state: New Mexico
city: Bronx
country: United States
state: New York
city: Memphis
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Galveston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Temple
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
Study officials:
affiliation: Genentech, Inc.
name: Harald Weber, M.D.
role: STUDY_DIRECTOR
References: