Radiation Therapy, Pemetrexed Disodium, and Carboplatin in Treating Patients With Locally Advanced Esophageal Cancer That Can Be Removed By Surgery

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as pemetrexed disodium and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving radiation therapy together with pemetrexed disodium and carboplatin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well giving radiation therapy together with pemetrexed disodium and carboplatin works in treating patients with locally advanced esophageal cancer that can be removed by surgery.

Detailed Description
-----------------
OBJECTIVES: Primary * Determine the pathologic complete response rate of radiotherapy, pemetrexed disodium, and carboplatin when administered prior to esophagectomy in patients with locally advanced esophageal cancer. Secondary Determine the activity, in terms of clinical response rate and adverse event profile of radiotherapy, pemetrexed disodium, and carboplatin when administered prior to esophagectomy. Determine the overall survival, time-to-progression, and time-to-treatment failure for patients receiving the above combined modality treatment. Determine the surgical outcome for all patients who undergo esophagectomy. Determine the time-to-disease recurrence and disease-free survival for patients who have a curative resection. Determine quality of life of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients undergo radiotherapy once daily, 5 days a week, for 5 ½ weeks and concurrently receive pemetrexed disodium IV over 10 minutes and carboplatin IV over 30 minutes on days 1 and 22. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who are eligible will undergo esophagectomy between 4-12 weeks after completion of radiotherapy. Quality of life is assessed at baseline, immediately prior to day 22 of chemotherapy, and within 2 weeks prior to surgery. After completion of study treatment, patients are followed periodically for approximately 4 years. PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Official Title
-----------------
A Phase II Trial of Preoperative Radiation and Chemotherapy (Pemetrexed and Carboplatin) for Locally Advanced Esophageal Cancer

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

Intervention / Treatment
-----------------
* Drug: carboplatin
* Drug: Pemetrexed
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal (GE) junction No T1-2, N0, M0 disease No palpable or biopsy-proven involvement of supraclavicular nodes or radiographically involved supraclavicular nodes (> 1.5 cm in greatest dimension) for lesions in mid-thoracic, distal thoracic, or GE junction + Supraclavicular node involvement allowed provided there are upper thoracic esophagus primary lesions Patients with involvement of celiac nodes (stations 15-20) are eligible if the primary lesion is mid-thoracic, distal esophagus, or GE junction No evidence of distant metastases Tumor must be considered surgically resectable - Patients with T4, N0 tumors that are potentially resectable are eligible No clinically relevant pleural or peritoneal effusion that is not amenable to drainage PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Life expectancy ≥ 12 weeks Absolute neutrophil count ≥1,500/mm^3 Platelet count ≥100,000/mm^3 Hemoglobin ≥10 g/dL Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST ≤ 3 times ULN Creatinine clearance ≥ 45 mL/min No New York Heart Association class III or IV congestive heart failure Pregnant or nursing women are ineligible Negative pregnancy test Fertile patients must use effective contraception No uncontrolled infection No other severe underlying disease that would preclude study entry No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ No prior sensitivity or allergic reaction to pemetrexed disodium or carboplatin Able to swallow pills PRIOR CONCURRENT THERAPY: No prior chemotherapy for esophageal cancer No prior radiotherapy field that overlapped the anticipated fields of study radiotherapy No prior radiotherapy to > 30% of the marrow cavity Patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) must be able to discontinue use 2 days prior, during, and 2 days after pemetrexed disodium administration (5 days prior for long-life NSAIDs) Patients must not have been receiving cyclooxygenase-2 inhibitors at study entry and while receiving protocol therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 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/Carboplatin<br>Pemetrexed+Carboplatin+Radiation | Drug: carboplatin<br>* carboplatin is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment.<br>Drug: Pemetrexed<br>* Pemetrexed is to be given on days 1 and 22 of the 5 ½ weeks of radiation treatment.<br>Procedure: conventional surgery<br> <br> Procedure: neoadjuvant therapy<br> <br> Radiation: radiation therapy<br>* Radiation therapy begins day 1 and continues for 5 ½ weeks (45 Gy in 22-25 fractions of 1.8 Gy to extended field; 50.4 Gy in 28 fractions within boost field).<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response Rate | The proportion of pathologic complete responses will be estimated by the number of pathologic complete responses divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true pathologic complete response rate will be calculated. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for Measurable disease is defined as at least one lesion whose longest diameter can be accurately measured as ≥2.0 cm with conventional techniques or as ≥1.0 cm with spiral CT. Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined and surrounded by aerated lung. However, CT is preferable. | Baseline to time of surgery (around 10 - 18 weeks post-baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time from registration to death due to any cause. | From baseline to 4 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenocarcinoma of the esophagus, squamous cell carcinoma of the esophagus, stage III esophageal cancer, stage II esophageal cancer