Lapatinib With Carboplatin and Paclitaxel in Esophagus and Gastroesophageal Junction (GEJ)
RATIONALE: Since lapatinib inhibits both EGFR and HER2 receptors, it is an attractive agent for the treatment of esophageal and GEJ tumors.
PURPOSE: Lapatinib is currently approved for HER2 positive metastatic breast cancer in combination with capecitabine or letrozole. It is hoped that by giving lapatinib and carboplatin and paclitaxel together, their combined effects will further slow or stop the cancer cells from growing.
Adenocarcinoma of the Esophagus
Adenocarcinoma of the Gastroesophageal Junction
Drug: Carboplatin AUC
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Pilot Study of Lapatinib in Combination With Carboplatin and Paclitaxel in the Treatment of Recurrent/Metastatic Adenocarcinoma of the Esophagus and Gastroesophageal Junction (GEJ)|
- PHASE I:Number of patients that experience a grade 3-4 dose limiting toxicity [ Time Frame: after 9 weeks (3 cycles) of treatment ] [ Designated as safety issue: Yes ]A dose limiting toxicity (DLT) will be defined as any grade 3-4 non-hematologic toxicity or increase in bilirubin >/= 2 mg/dL (>2X baseline in patients with Gilbert's syndrome), or elevation in AST/ALT > 3.0 X ULN during the first 3 week course of therapy.
- PHASE II: To assess the response rate to this regimen. [ Time Frame: after 37 months ] [ Designated as safety issue: No ]Patients with stable or responding disease after 6 cycles of carboplatin and paclitaxel will continue treatment with lapatinib alone until progression of disease or intolerable side effects.
- To determine the overall survival [ Time Frame: after 37 months ] [ Designated as safety issue: No ]Overall survival is defined as the length of time between the date of starting treatment and death due to any cause. For a patient who is alive at the time of the statistical analysis, the patient will be considered censored at the last date of known contact.
|Study Start Date:||August 2011|
|Estimated Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
|Experimental: Lapatinib With Carboplatin and Paclitaxel||
Drug: Carboplatin AUC
Carboplatin AUC 6 IV over 30 minutes on day one of a three week cycle. This will be continued for 6 cycles or until progression of disease or intolerable side effects.Drug: Paclitaxel
Paclitaxel 175 mg/m2 IV over 3 hours day one of a three week cycle. This will be continued for 6 cycles or until progression of disease or intolerable side effects.Drug: lapatinib
Lapatinib should be taken once daily, at the same time daily, on an empty stomach, either 1 hour before, or 1 hour after meals.
- Phase I: To assess the toxicity and feasibility of the addition of lapatinib to carboplatin and paclitaxel in patients with recurrent/metastatic adenocarcinoma of the esophagus and gastroesophageal junction.
- Phase II: To assess the response rate to this regimen.
There will be an initial phase I safety cohort studies requiring up to 12 patients, followed by a phase II cohort using the lapatinib dose defined in phase I. Carboplatin and paclitaxel doses will not be escalated.
The initial dose of lapatinib of 750 mg daily by mouth will be given to 6 patients. There will be no dose escalation of the lapatinib above 1000 mg daily. The lapatinib dose for the phase II cohort of this trial will be based only on toxicities experienced during the first cycle (3 weeks) of treatment.
- Phase II: Once the optimal lapatinib dose has been chosen, all remaining patients will initiate treatment at this dose level. Patients with stable or responding disease after 6 cycles will continue treatment with lapatinib alone until progression of disease or intolerable side effects. Feasibility, toxicity and response rate of this combination will be assessed.
PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01395537
|United States, Ohio|
|Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44016|
|Principal Investigator:||David Adelstein, MD||Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Principal Investigator:||Neelesh Sharma, MD||Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center|