Study of 5-FU, Oxaliplatin, & Lapatinib Combined With Radiation Therapy to Treat HER2 Positive Esophagogastric Cancer
|HER2 Positive Esophagogastric Cancer||Drug: 5-Fluorouracil Drug: Oxaliplatin Drug: Lapatinib Radiation: Radiation Therapy||Phase 2|
|Study Design:||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 ]Defined as the absence of invasive tumor in esophagogastric and lymph node tissue removed at time of surgery, as judged by the local pathologist. An improvement in pCR rate from 30 percent (historical) to 50 percent is the primary efficacy endpoint.
- Safety and Optimal Dose of Regimen [ Time Frame: 18 months ]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 ]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 ]Defined as the frequency of adverse events for patients who received at least one dose of study treatment, and assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.
- Time to Progression (TTP) [ Time Frame: 18 months ]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 ]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|