Combination of Weekly Paclitaxel With Neratinib and Trastuzumab in Women With Metastatic HER2-positive Breast Cancer
The FB-8 study is designed as an open label, single arm, Phase I dose-escalation study evaluating the combination of weekly paclitaxel with neratinib and trastuzumab in women with metastatic, HER2-positive breast cancer. The primary aim of this study is to determine the safety and tolerability of the three-drug combination.
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose-Escalation Study Evaluating the Combination of Weekly Paclitaxel With Neratinib and Trastuzumab in Women With Metastatic HER2-positive Breast Cancer|
- Safety and tolerability of the three-drug combination [ Time Frame: Through 6 months after last dose ] [ Designated as safety issue: Yes ]Number of patients experiencing dose limiting toxicities (DLT).
- Overall response rate [ Time Frame: Measured at 24 weeks from start of therapy. ] [ Designated as safety issue: No ]Number of patients with disappearance of all target lesions; Number of patients with at least a 30% decrease in the sum of the longest diameter (LD) of target lesions; patients with neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as a reference the smallest sum LD since baseline.
- Progression-free interval [ Time Frame: Time to disease progression up to 15 months. ] [ Designated as safety issue: No ]Number of patients with at least a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since baseline or the appearance of one or more new lesions.
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||August 2013|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Paclitaxel (80 mg/m2 IV on days 1, 8, and 15 every 28 days) and trastuzumab (4 mg/kg/ loading dose, then 2 mg/kg) IV weekly beginning on day 1 of paclitaxel, neratinib orally daily beginning on day 1 of paclitaxel until disease progression.
80 mg/m2 IV on days 1, 8, and 15 every 28 days until disease progression.Biological: trastuzumab
4 mg/kg IV loading dose, then 2 mg/kg IV weekly until disease progression.Drug: Neratinib
Dose level 1: 120 mg/day orally; Dose level 2: 160 mg/day orally; Dose level 3: 240 mg/day orally; Dose level 4: 200 mg/day orally.
Patients will receive concurrent therapy with paclitaxel (80 mg/m2 IV on days 1, 8, and 15 of a 28-day cycle), trastuzumab (4 mg/kg IV loading dose, then 2 mg/kg IV weekly), and neratinib. The neratinib dose-escalation will include 4 dose levels (120 mg, 160 mg, 200 mg, and 240 mg) as a daily oral dose.
The neratinib dose-escalation for the study will proceed on the basis of dose-limiting toxicity (DLT) during cycle 1. DLT will be defined as the occurrence of 1 or more of the following events during cycle 1: any grade diarrhea that is associated with fever or dehydration; grade 3 diarrhea lasting more than 2 days on optimal medical therapy; grade 4 diarrhea of any duration; grade 3 or 4 neutropenia associated with fever; grade 4 neutropenia lasting more than 7 days; grade 4 thrombocytopenia; grade 3 or 4 non-hematological toxicity; or any toxicity-related delay of more than 2 weeks to initiate cycle 2. Patients will be enrolled at the next dose level when all evaluable patients at the same dose level have completed the first treatment cycle. Enrolled patients will remain on the assigned dose level treatment until toxicity or disease progression.
|United States, New Jersey|
|Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08901|
|United States, Pennsylvania|
|NSABP Foundation, Inc.|
|Pittsburgh, Pennsylvania, United States, 15212|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15232-1305|
|United States, West Virginia|
|West Virginia University Hospitals|
|Morgantown, West Virginia, United States, 26506-9162|
|Principal Investigator:||Norman Wolmark, MD||NSABP Foundation, Inc.|