Bortezomib, Paclitaxel, and Carboplatin in Treating Patients With Unresectable, Metastatic Cancer of the Esophagus or Gastroesophageal Junction

Study Overview
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Brief Summary
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RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with paclitaxel and carboplatin may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bortezomib together with paclitaxel and carboplatin works in treating patients with unresectable, metastatic cancer of the esophagus or gastroesophageal junction.

Detailed Description
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OBJECTIVES: Primary Determine the confirmed tumor response rate in patients with unresectable, metastatic adenocarcinoma of the esophagus, gastroesophageal junction, or gastric cardia treated with bortezomib, paclitaxel, and carboplatin. Secondary Determine the time to tumor progression, overall survival, and duration of response in patients treated with this regimen. Determine the adverse events in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive bortezomib IV over 3-5 seconds on days 1, 4, and 8 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 2. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years. PROJECTED ACCRUAL: A total of 25-60 patients will be accrued for this study within 17 months.

Official Title
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A Phase II Trial of PS-341 in Combination With Paclitaxel and Carboplatin for Metastatic Adenocarcinoma of the Lower Esophagus, Gastroesophageal Junction, and Gastric Cardia

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: bortezomib
* Drug: carboplatin
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of 1 of the following sites: Esophagus Gastroesophageal junction Gastric cardia No greater than 2 cm from the gastroesophageal junction into the stomach Unresectable, metastatic disease Not a candidate for potentially curative therapy AND no other more reasonable potentially curative conventional therapy exists At least 1 measurable lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan No known CNS metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 12 weeks Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin normal AST ≤ 3 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2 times ULN Renal Creatinine ≤ 1.5 times ULN Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for up to 6 months after completion of study treatment No peripheral neuropathy ≥ grade 2 No uncontrolled infection No chronic debilitating disease No prior allergic reaction to carboplatin or paclitaxel No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy No prior immunotherapy for recurrent or metastatic disease No prior biologic therapy for recurrent or metastatic disease No concurrent prophylactic colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF]) Chemotherapy No prior chemotherapy for recurrent or metastatic disease Prior chemotherapy in the neoadjuvant or adjuvant setting (after complete resection of the original tumor) allowed Prior combination chemotherapy and radiotherapy allowed provided patient achieved a complete response AND the last dose of combination therapy was administered ≥ 6 months ago Endocrine therapy Not specified Radiotherapy See Chemotherapy No prior radiotherapy for recurrent or metastatic disease Prior radiotherapy in the neoadjuvant or adjuvant setting (after complete resection of the original tumor) allowed No prior radiotherapy to > 25% of bone marrow for locally advanced disease More than 4 weeks since prior radiotherapy Surgery More than 4 weeks since prior open abdominal exploration (e.g., laparotomy) More than 2 weeks since prior minimally invasive procedures (e.g., laparoscopy)

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: bortezomib + paclitaxel + carboplatin<br>Patients receive bortezomib IV over 3-5 seconds on days 1, 4, and 8 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 2. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years. | Drug: bortezomib<br> <br> Drug: carboplatin<br> <br> Drug: paclitaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed tumor response rate |  | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to tumor progression |  | Up to 3 years | 
| Overall survival |  | Up to 3 years | 
| Duration of response |  | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the esophagus, stage IV esophageal cancer, recurrent esophageal cancer