A Phase II Study With Lead-in Safety Cohort of 5-Fluorouracil, Oxaliplatin and Lapatinib in Combination With Radiation Therapy as Neoadjuvant Treatment for Patients With Localized HER2 Positive Esophagogastric Adenocarcinomas
With the improvements in response rate and survival seen for HER2 positive patients with the
use of HER2 blockade in the metastatic setting, the use of HER2 blockade in the neoadjuvant
setting to increase antitumor effect is promising.
This study will be carried out in two parts, a lead-in safety cohort and Phase II. During
the lead-in portion approximately 12 patients will receive neoadjuvant treatment with
5-fluorouracil (5-FU), oxaliplatin, lapatinib, and radiation therapy to evaluate the safety
of the combination. For the lead-in portion, the initial dose of lapatinib will be 1000 mg
QD. If this dose is tolerated, the lapatinib dose will be increased to 1250 mg QD and
tolerability will be reassessed. If there are no unacceptable toxicities, phase II
enrollment will proceed at a dose of 1250 mg QD. If unacceptable toxicities are encountered
at both 1000 and 1250 mg QD, a lower dose of 750 mg QD may be evaluated.
Following the lead-in cohort, the Phase II portion will commence and up to 30 additional
patients may be treated. The starting doses will be administered as follows:
5-FU 225 mg/mg2 continuous intravenous (IV) infusion Days 1 - 42 during XRT Oxaliplatin 85
mg/m2 Days 1, 15 and 29, given by IV infusion, per institutional standard Lapatinib
Continuous PO daily dosing during XRT (final dose determined during lead-in cohort)
Lapatinib will be self-administered (by the patient) on a continuous daily dosing schedule.
Lapatinib should be taken at approximately the same time each day. Lapatinib should be taken
with a glass of water; the entire dose should be taken over as short a time as possible.
Patients should be instructed to swallow the capsules as a whole and not to chew or crush
Slurry preparation of lapatinib will be permitted for patients with a gastrostomy tube in
place. See Section 8.1.2 for slurry preparation instructions.
If vomiting occurs, no attempt should be made to replace the vomited dose. Lapatinib dosing
compliance should be reviewed with the patient during treatment visits occurring during
weeks 1-6. Missed doses will be documented.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Pathologic Complete Response Rate (pCR rate)
This trial seeks to evaluate the pathological complete response (pCR) rate of the combination of lapatinib and chemoradiation as neoadjuvant treatment for patients with localized HER2 positive esophagogastric adenocarcinomas.
Johanna C Bendell, MD
Sarah Cannon Research Institute
United States: Food and Drug Administration
SCRI GI 166
|Northeast Georgia Medical Center||Gainesville, Georgia 30501|
|Grand Rapids Clinical Oncology Program||Grand Rapids, Michigan 49503|
|Chattanooga Oncology and Hematology Associates||Chattanooga, Tennessee 37404|
|Tennessee Oncology||Nashville, Tennessee 37203|
|Oncology Hematology Care||Cincinnati, Ohio 45242|
|Toledo Community Oncology Program||Toledo, Ohio 43617|
|Woodlands Medical Specialists||Pensacola, Florida 32503|