Study of 5-FU, Oxaliplatin, & Lapatinib Combined With Radiation Therapy to Treat HER2 Positive Esophagogastric Cancer
With improvements in response rate and survival seen for HER2 positive patients treated with HER2 blockade in the metastatic setting, the use of HER2 blockade in the neoadjuvant setting to increase antitumor effect shows promise. Patients with previously untreated localized HER2 positive esophageal, GE junction and gastric adenocarcinomas will be enrolled. Patients meeting all inclusion/exclusion criteria will receive neoadjuvant treatment with concurrent chemotherapy and radiation therapy beginning on day 1 of treatment. During the lead-in safety portion, the optimal dose of lapatinib will be determined.
HER2 Positive Esophagogastric Cancer
Radiation: Radiation Therapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Pathologic Complete Response Rate (pCR rate) [ Time Frame: 18 months ] [ Designated as safety issue: No ]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.
- Safety and optimal dose of regimen [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]An additional primary objective is to evaluate the safety and optimal dose of lapatinib when added to 5-FU, oxaliplatin and radiation therapy.
- Progression Free Survival (PFS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]Progression Free Survival will be evaluated for neoadjuvant patients treated with 5-FU, oxaliplatin, lapatinib and radiation therapy.
- Toxicity profile for neoadjuvant patients treated with 5-FU, Oxaliplatin, Lapatinib and radiation therapy [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]The toxicity assessments will be performed at week 4, once during week 8-10 and at the end of the study.
- Time to Progression (TTP) [ Time Frame: 18 months ] [ Designated as safety issue: No ]Time to Progression will be evaluated for neoadjuvant patients treated with 5-FU, oxaliplatin, lapatinib and radiation therapy.
- Overall Survival (OS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]Overall Survival will be evaluated for neoadjuvant patients treated with 5-FU, oxaliplatin, lapatinib and radiation therapy.
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||January 2015|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
5-FU, 225 mg/m2 IVCI, during XRT.
Other Name: Combined Modality TreatmentDrug: Oxaliplatin
Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
Other Name: Combined Modality TreatmentDrug: Lapatinib
Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Other Name: Combined Modality TreatmentRadiation: Radiation Therapy
Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
This is an open-label, non-randomized, Phase II study with a lead-in safety cohort. The study will evaluate the combination of 5-Fluorouracil, Oxaliplatin and Lapatinib with radiation therapy as neoadjuvant treatment for patients with previously untreated localized HER2 positive esophagogastric adenocarcinomas. Approximately 12 patients will be enrolled in the lead-in cohort to evaluate the safety of the combination. Following the lead-in cohort, Phase II 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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01769508
|Contact: Sarah Cannon Research Instituteemail@example.com|
|United States, Florida|
|Florida Cancer Specialists - South||Recruiting|
|Fort Myers, Florida, United States, 33916|
|Florida Hospital Cancer Institute||Recruiting|
|Orlando, Florida, United States, 32804|
|Woodlands Medical Specialists||Recruiting|
|Pensacola, Florida, United States, 32503|
|Florida Cancer Specialists-North||Recruiting|
|St. Petersburg, Florida, United States, 33705|
|United States, Georgia|
|Northeast Georgia Medical Center||Recruiting|
|Gainesville, Georgia, United States, 30501|
|United States, Michigan|
|Grand Rapids Oncology Program||Recruiting|
|Grand Rapids, Michigan, United States, 49503|
|United States, Ohio|
|Oncology Hematology Care||Recruiting|
|Cincinnati, Ohio, United States, 45242|
|United States, Tennessee|
|Chattanooga Oncology and Hematology Associates||Recruiting|
|Chattanooga, Tennessee, United States, 37404|
|Nashville, Tennessee, United States, 37203|
|Study Chair:||Johanna C Bendell, MD||SCRI Development Innovations, LLC|