A Phase II Study of Pemetrexed and Carboplatin in the Treatment of Esophageal Cancer

Study Overview
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Brief Summary
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This is a study of an investigational agent, pemetrexed, in combination with a standard chemotherapy drug, carboplatin, for treatment of patients with metastatic esophageal cancer.

Official Title
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A Phase II Study of Pemetrexed and Carboplatin in the Treatment of Esophageal Cancer

Conditions
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Esophageal Neoplasms

Intervention / Treatment
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* Drug: Pemetrexed
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a histologically or cytologically proven metastatic or recurrent esophageal cancer. Both adenocarcinoma and squamous carcinoma are eligible for the study. Patients with small cell carcinoma or sarcoma of the esophagus are not eligible for the study. Patients may have had no prior chemotherapy treatment for metastatic esophageal cancer. Patients may have had chemotherapy with 5-FU combined with definitive radiotherapy for curative intent in the adjuvant, neoadjuvant, or definite setting for locally advanced esophageal cancer, if no less than one year prior to trial enrollment. Patients may not have received pemetrexed in the past. Patients who have had radiotherapy for esophageal cancer must have completed radiotherapy at least four weeks prior to entry in the study. Patients need to have measurable disease. Lesions that are not considered measurable include the following: Bone lesions Brain metastases or leptomeningeal disease Ascites Pleural/pericardial effusion Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Tumor lesions situated in a previously irradiated area ECOG) performance status of 0-2. Life expectancy of >=12 weeks. Patients must have adequate bone marrow function defined as: white blood cells (WBC) >= 3000/mm^3, absolute neutrophil count (ANC) >= 1,500/mm^3, hemoglobin >= 9.0 g/dL, and platelet count >= 100,000/mm^3. Patients must have adequate liver function defined as: Bilirubin <= 1.5 x institutional normal and ALT/AST < 3 x institutional normal. Patients must have adequate renal function defined as: serum creatinine <= 3.0 mg/dL and creatinine clearance >= 45 mL/min. Radiation therapy for brain metastases should be completed at least four weeks prior to enrollment to this protocol. Patients must have recovered from uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or uncontrolled symptomatic cardiac arrhythmia. Patients must be able to be compliant with premedications of dexamethasone, folic acid, and vitamin B12. For all sexually active women of child-bearing age, the use of adequate contraception (hormonal or barrier method of birth control) will be required prior to study entry and for the duration of study participation. Age >= 18 years. Written consent. Ibuprofen (400 mg qid) can be administered with Alimta in patients with normal renal function (creatinine clearance > 80 mL/min Exclusion Criteria: Patients with third-space fluid (pleural effusions, ascites, etc.) uncontrolled by drainage. Pregnant or nursing females Patients who have had pre-existing neuropathy greater than or equal to grade 2. Patients with known active CNS metastases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed + Carboplatin<br>Pemetrexed 500 mg/m^2 IV over 10 minutes Carboplatin AUC 5 IV over 30 minutes on day 1 of each cycle Each cycle will last 21 days. | Drug: Pemetrexed<br> <br> Drug: Carboplatin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall response rate = complete response (CR) + partial response (PR) using RECIST. CR=disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level PR=at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD | Until patient progresses or dies (median follow-up 293 days -- range (63-632 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression | -Progressive disease=at least a 20% increase in the sum of the LD of the target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions | Until patient progresses (median follow-up 293 days -- range (63-632 days) | 
| Overall Survival Rate |  | 1 year | 
| Toxicities |  | 30 days following completion of treatment (maximum number of cycles = 6) | 
| Overall Survival Rate |  | 2 years | 
| Overall Survival (OS) | OS is defined as the time from initiation of treatment to the date of any reason death while those living subjects will be censored at the last assessment date. | Until patient's death (median follow-up 293 days -- range (63-632 days)) |