Clinical trial NCT00005599: Bryostatin 1 Plus Paclitaxel in Treating Patients With Locally Advanced or Metastatic Esophageal Cancer or Stomach Cancer
Official title: Phase II Trail of Bryostatin-1 and Paclitaxel in Patients With Advanced Esophageal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Gastric Cancer
Keywords: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Albert Einstein Clinical Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Gary K. Schwartz, MD
role: STUDY_CHAIR
References:
citation: Ku GY, Ilson DH, Schwartz LH, Capanu M, O'Reilly E, Shah MA, Kelsen DP, Schwartz GK. Phase II trial of sequential paclitaxel and 1 h infusion of bryostatin-1 in patients with advanced esophageal cancer. Cancer Chemother Pharmacol. 2008 Oct;62(5):875-80. doi: 10.1007/s00280-008-0677-y. Epub 2008 Feb 13.