Pemetrexed, Cisplatin, and Radiation Therapy in Treating Patients With Esophageal or Gastroesophageal Junction Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Cisplatin may make tumor cells more sensitive to radiation therapy. Giving pemetrexed together with cisplatin and radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of pemetrexed when given together with cisplatin and radiation therapy in treating patients with stage III or stage IV esophageal cancer or gastroesophageal junction cancer.

Detailed Description
-----------------
OBJECTIVES: Primary To establish the maximum tolerated dose of pemetrexed disodium in combination with cisplatin and standard-dose radiotherapy in patients with stage III or IV esophageal or gastroesophageal junction carcinoma. Secondary To specifically characterize the toxicity profile of this regimen. To investigate, preliminarily, the anti-tumor activity of this regimen, as measured by standard response criteria (RECIST criteria), in patients with measurable disease. OUTLINE: This is a dose-escalation study of pemetrexed disodium. Patients receive pemetrexed disodium IV over 10 minutes on days 1, 15, and 29 and cisplatin IV over 10 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external beam radiotherapy once daily, 5 days a week, for up to 6 weeks. After completion of study therapy, patients are followed for 30 days and then every 3 months for 1 year.

Official Title
-----------------
Phase I Study of Concomitant Pemetrexed and CDDP Plus Radiation Therapy in Patients With Locally Advanced or Metastatic Esophageal or Gastroesophageal (GEJ) Carcinomas

Conditions
-----------------
Esophageal Cancer

Intervention / Treatment
-----------------
* Drug: cisplatin
* Drug: Pemetrexed
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Diagnosis of esophageal or gastroesophageal junction carcinoma Stage III or IV disease Treatment with chemoradiotherapy is considered appropriate Measurable or evaluable disease Clinically significant pleural or pericardial effusions or ascites allowed provided they were drained prior to study entry No pleurodesis within the past 2 weeks Controlled brain metastasis allowed provided patient is clinically stable with no signs of progression by MRI or CT scan of the brain ≥ 60 days after completion of treatment AND is asymptomatic and does not require steroids PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 12 weeks WBC ≥ 2,500/mm^3 ANC ≥ 1,500/mm^3 Hemoglobin ≥ 9 g/dL Platelet count ≥ 100,000/mm^3 Total bilirubin normal Alkaline phosphatase AND AST and ALT meeting the following criteria: Alkaline phosphatase normal AND AST or ALT ≤ 3 times upper limit of normal (ULN) (≤ 5 times ULN for patients with liver metastases) Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN Alkaline phosphatase ≤ 5 times ULN AND AST or ALT normal Creatinine clearance ≥ 45 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study therapy Able to take folic acid, vitamin B_12, or corticosteroids No known severe hypersensitivity reaction to study drugs No uncontrolled serious active infection No pre-existing peripheral neuropathy > grade 1 No significant cardiac disease, including any of the following: Uncontrolled high blood pressure Unstable angina Congestive heart failure within the past 6 months Left ventricular ejection fraction below the lower limit of normal Myocardial infarction within the past year Serious cardiac arrhythmias requiring medication PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior systemic therapy regimens No prior radiotherapy to gastric/esophageal fields No aspirin or other NSAID before and after pemetrexed disodium administration No concurrent colony-stimulating factors (CSF) to maintain WBC and ANC eligibility values

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed, Cisplatin, Radiation Therapy<br>Concomitant Pemetrexed and CDDP Plus Radiation Therapy | Drug: cisplatin<br>* Standard weekly dose<br>* Other names: CDDP;Drug: Pemetrexed<br>* Biweekly pemetrexed dose escalation<br>* Other names: Pemetrexed disodium;Radiation: radiation therapy<br>* Weekly standard dose radiation therapy<br>* Other names: RT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The maximum tolerated dose (MTD) of pemetrexed |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity profile |  | 12 months | 
| Response (complete response, partial response, progressive disease, and stable disease) as measured by RECIST criteria |  | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage III esophageal cancer, stage IV esophageal cancer