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

NCT00927589 | Completed Phase 1 Results

• 2 other identifiers: H4613gGO01305
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 20

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.

Conditions

Solid Cancers

Keywords

HER2+ Metastatic Cancer; HER2+ Locally Advanced Inoperable Cancer; HER2+ Solid Malignancy

Outcome Measures

Primary Outcomes (10)

• Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) at Trastuzumab Steady State

  Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Trastuzumab steady state was defined as the average of the 2 ECG measurements collected on Cycle 1 Day 8 (C1D8) and Cycle 2 Day 1 (C2D1) after the trastuzumab infusion.

  Baseline, Cycle 1 Day 8 and Cycle 2 Day 1

• Maximum Observed Plasma Concentration (Cmax) of Carboplatin

  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)

• Area Under the Curve From Time Zero to 6 Hours Post Infusion (AUC0-6hr) of Carboplatin

  AUC0-6hr = Area under the plasma concentration versus time curve from 0 to 6 hours post-infusion.

  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)

• Dose-Normalized Cmax (Cmax/D) of Carboplatin

  Dose normalized Cmax is the maximum observed concentration of carboplatin in plasma normalized for different dose levels.

  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)

• Geometric Mean Ratio of Cmax/D of Carboplatin

  The geometric mean ratio of Cmax of carboplatin was defined as the Cmax/D of carboplatin on Cycle 1 Day 1 (in the absence of trastuzumab) divided by Cmax/D of carboplatin on Cycle 2 Day 1 (in the presence of trastuzumab).

  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)

• Dose-Normalized AUC0-6hr (AUC0-6hr/D) of Carboplatin

  AUC0-6hr/D = Area under the plasma concentration versus time curve from 0 to 6 hours post-infusion, normalized by carboplatin dose level.

  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)

• Geometric Mean Ratio of AUC0-6hr/D of Carboplatin

  The geometric mean ratio of AUC0-6hr/D of carboplatin was defined as the AUC0-6hr/D of carboplatin on Cycle 1 Day 1 (in the absence of trastuzumab) divided by AUC0-6hr/D of carboplatin on Cycle 2 Day 1 (in the presence of trastuzumab).

  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)

• Plasma Decay Half-Life (t1/2) of Carboplatin

  Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  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)

• Maximum Observed Serum Concentration (Cmax) of Trastuzumab

  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

• Minimum Observed Serum Trough Concentration (Cmin) of Trastuzumab

  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 (10)

• Change From Baseline in Corrected QT Interval Using Bazett's Correction (QTcB) at Trastuzumab Steady State

  Baseline, Cycle 1 Day 8 and Cycle 2 Day 1

• Baseline-adjusted QTcF, QTcB, PR Interval, and QRS Duration

  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)

• Baseline-adjusted Heart Rate

  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)

• Number of Participants Within Each Absolute QTc Interval Category

  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)

• Number of Participants With Increase From Baseline in QTc Interval

  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)

Study Arms (1)

1

EXPERIMENTAL

Drug: carboplatin; Drug: docetaxel; Drug: trastuzumab

Interventions

carboplatin DRUG

Intravenous repeating dose

1

docetaxel DRUG

Intravenous repeating dose

1

trastuzumab DRUG

Intravenous repeating dose

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (20)

Unknown Facility

Scottsdale, Arizona, 85258, United States

Location

Unknown Facility

Beverly Hills, California, 90211, United States

Location

Unknown Facility

La Jolla, California, 92093, United States

Location

Unknown Facility

San Diego, California, 92123, United States

Location

Unknown Facility

Santa Rosa, California, 95403, United States

Location

Unknown Facility

Whittier, California, 90603, United States

Location

Unknown Facility

Miami, Florida, 33136, United States

Location

Unknown Facility

Wichita, Kansas, 67214-3728, United States

Location

Unknown Facility

Billings, Montana, 59101, United States

Location

Unknown Facility

Farmington, New Mexico, 87401, United States

Location

Unknown Facility

The Bronx, New York, 10461, United States

Location

Unknown Facility

Memphis, Tennessee, 38120, United States

Location

Unknown Facility

Nashville, Tennessee, 37232, United States

Location

Unknown Facility

Dallas, Texas, 75230, United States

Location

Unknown Facility

Galveston, Texas, 77555, United States

Location

Unknown Facility

Houston, Texas, 77024, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

Unknown Facility

Temple, Texas, 76508, United States

Location

Unknown Facility

Seattle, Washington, 98101, United States

Location

MeSH Terms

Interventions

Carboplatin; Docetaxel; Trastuzumab

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Harald Weber, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2009
• First Posted: June 25, 2009
• Study Start: July 1, 2009
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: December 10, 2015
• Results First Posted: December 10, 2015

Record last verified: 2015-11

Locations

US (20)