Study With Lead-in Cohort of 5-FU, Oxaliplatin, Lapatinib & 5-FU for Patients With HER2 Positive Esophagogastric Cancer
This is an open-label, non-randomized, Phase II study with a lead-in safety cohort (see Figure 1). 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.
Localized 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 2014 (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
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 them.
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.
|Contact: Trial Informationfirstname.lastname@example.org|
|United States, Florida|
|Florida Cancer Specialists - South||Recruiting|
|Fort Myers, Florida, United States, 33916|
|Contact: Cara O'Keefe 239-274-9930|
|Woodlands Medical Specialists||Recruiting|
|Pensacola, Florida, United States, 32503|
|Contact: Leslie Bellamy email@example.com|
|Principal Investigator: Rami Owera, MD|
|Florida Cancer Specialists-North||Recruiting|
|St. Petersburg, Florida, United States, 33705|
|Contact: Christine Biermeir firstname.lastname@example.org|
|Principal Investigator: Peter Acs, MD|
|United States, Georgia|
|Northeast Georgia Medical Center||Recruiting|
|Gainesville, Georgia, United States, 30501|
|Contact: Patti Rotunda 770-219-8826 email@example.com|
|Principal Investigator: Andre Kallab, MD|
|United States, Ohio|
|Oncology Hematology Care||Recruiting|
|Cincinnati, Ohio, United States, 45242|
|Contact: Research Coordinator 513-891-4800 firstname.lastname@example.org|
|United States, Tennessee|
|Chattanooga Oncology and Hematology Associates||Recruiting|
|Chattanooga, Tennessee, United States, 37404|
|Contact: Research Coordinator 423-698-1844|
|Nashville, Tennessee, United States, 37203|
|Contact: Trials Information 615-329-7274 email@example.com|
|Study Chair:||Johanna C Bendell, MD||SCRI Development Innovations, LLC|