Bryostatin 1 Plus Paclitaxel in Treating Patients With Locally Advanced or Metastatic Esophageal Cancer or Stomach Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of bryostatin 1 and paclitaxel in treating patients who have locally advanced or metastatic esophageal cancer or stomach cancer.

Detailed Description
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OBJECTIVES: Determine the complete and partial response rates in patients with unresectable or metastatic esophageal cancer or carcinoma of the gastroesophageal junction treated with sequential paclitaxel and bryostatin 1. Determine the toxicity of this regimen in this patient population. Determine the survival of patients after treatment with this regimen. Determine the quality of life of patients treated with this regimen. Examine pre- and post-treatment tissue biopsies for markers of apoptosis in selected patients. OUTLINE: This is a multicenter study. Patients receive paclitaxel IV over 1 hour on day 1 and bryostatin 1 IV over 24 hours on day 2 weekly for 2 weeks. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Quality of life is assessed at baseline, after courses 1 and 2, and then after every 2 courses thereafter. PROJECTED ACCRUAL: A total of 19-33 patients will be accrued for this study within 1-2 years.

Official Title
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Phase II Trail of Bryostatin-1 and Paclitaxel in Patients With Advanced Esophageal Cancer

Conditions
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Esophageal Cancer, Gastric Cancer

Intervention / Treatment
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* Drug: bryostatin 1
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or carcinoma of the gastroesophageal (GE) junction If tumor extends below GE junction into the proximal stomach, 50% of the tumor must involve the esophagus or GE junction No gastric cancer with only a minor involvement of GE junction or distal esophagus Locally advanced and considered surgically unresectable or metastatic Measurable disease Accurately measured in at least 1 dimension as at least 20 mm with conventional techniques or at least 10 mm with spiral CT scan No truly nonmeasurable lesions only: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusions Inflammatory breast disease Lymphangitis cutis/pulmonis Abdominal masses not confirmed and followed by imaging techniques Cystic lesions No brain metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: Granulocyte count at least 1,500/mm^3 Platelet count at least 150,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL Renal: Creatinine no greater than 1.5 mg/dL Cardiovascular: No history of active angina No myocardial infarction within the past 6 months No history of significant ventricular arrhythmia requiring medication with antiarrhythmics Well-controlled atrial fibrillation on standard management allowed Pulmonary: DLCO at least 60% Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 2 months after study participation No preexisting neurotoxicity of grade 3 or greater No serious concurrent infection or nonmalignant medical illness that is uncontrolled or whose control may be jeopardized by complications of study therapy No concurrent psychiatric disorders that would preclude study compliance No other active malignancy within the past 5 years except: Nonmelanoma skin cancer Carcinoma in situ of the cervix History of T1a or b prostate cancer (detected incidentally at transurethral resection of prostate [TURP] and comprising less than 5% of resected tissue) provided prostate-specific antigen remained normal since TURP removal HIV negative No other concurrent medical condition that would preclude study therapy PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Chemotherapy: Recovered from prior chemotherapy No more than 1 prior neoadjuvant or adjuvant regimen for esophageal cancer No prior taxanes for esophageal cancer No prior bryostatin 1 for esophageal cancer No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: Prior radiotherapy allowed provided recent evidence of disease progression if indicator lesion is within prior radiation field Recovered from prior radiotherapy No concurrent radiotherapy Surgery: Not specified

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: bryostatin 1|nan|
|Drug: paclitaxel|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

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