Study of 5-FU, Oxaliplatin, & Lapatinib Combined With Radiation Therapy to Treat HER2 Positive Esophagogastric Cancer
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 ]The Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
- Toxicity Profile for Treated Patients [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]Treatment-related adverse events occurring in ≥ 15% of patients
- Time to Progression (TTP) [ Time Frame: 18 months ] [ Designated as safety issue: No ]Time to progression is defined as the time between day 1 cycle 1 and time to first documented disease progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
- Overall Survival (OS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
|Study Start Date:||February 2013|
|Study Completion Date:||February 2015|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Experimental: Combined Therapy
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
|United States, Florida|
|Florida Cancer Specialists - South|
|Fort Myers, Florida, United States, 33916|
|Florida Hospital Cancer Institute|
|Orlando, Florida, United States, 32804|
|Woodlands Medical Specialists|
|Pensacola, Florida, United States, 32503|
|Florida Cancer Specialists-North|
|St. Petersburg, Florida, United States, 33705|
|United States, Georgia|
|Northeast Georgia Medical Center|
|Gainesville, Georgia, United States, 30501|
|United States, Michigan|
|Grand Rapids Oncology Program|
|Grand Rapids, Michigan, United States, 49503|
|United States, Ohio|
|Oncology Hematology Care|
|Cincinnati, Ohio, United States, 45242|
|United States, Tennessee|
|Chattanooga Oncology and Hematology Associates|
|Chattanooga, Tennessee, United States, 37404|
|Nashville, Tennessee, United States, 37203|
|Study Chair:||Johanna C Bendell, MD||SCRI Development Innovations, LLC|