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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

Conditions: Gastric Cancer; Esophageal Cancer

Treatments: Drug: bryostatin 1; Drug: paclitaxel

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00005599

MSKCC-FDR001826

MSKCC-99094

CDR0000067712

NCI-250

Details and patient eligibility

About

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.

Full description

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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