Bryostatin 1 and Cisplatin in Treating Patients With Metastatic or Unresectable Stomach Cancer

Study Overview
=================
Brief Summary
-----------------
Phase II trial to study the effectiveness of bryostatin 1 and cisplatin in treating patients who have metastatic or unresectable stomach cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bryostatin 1 may increase the effectiveness of cisplatin by making tumor cells more sensitive to the drug. Combining cisplatin with bryostatin 1 may kill more tumor cells.

Detailed Description
-----------------
OBJECTIVES: I. Determine the response rate and survival in patients with metastatic or unresectable carcinoma of the stomach treated with bryostatin 1 and cisplatin. II. Determine the toxic effects of this regimen in these patients. III. Determine the molecular determinants of response to this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive bryostatin 1 IV over 72 hours on days 1-3 followed by cisplatin IV over 1 hour on day 4. Treatment repeats every 3 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity.

Official Title
-----------------
A Phase II Combination Trial of Bryostatin-1 and Cisplatin in the Treatment of Metastatic Gastric Cancer

Conditions
-----------------
Stage III Gastric Cancer, Stage IV Gastric Cancer

Intervention / Treatment
-----------------
* Drug: bryostatin 1
* Drug: cisplatin
* Other: laboratory biomarker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of metastatic or unresectable carcinoma of the stomach Measurable disease No brain metastasis Performance status - Karnofsky 70-100% More than 3 months WBC at least 3,000/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10 g/dL No history of any bleeding disorders Bilirubin no greater than 1.5 mg/dL Transaminases no greater than 2 times normal Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 60 mL/min No history of peptic ulceration or gastrointestinal bleeding No active infection No seizure disorder Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No other serious concurrent illness that would preclude study entry No medical, social, or psychological factors that would preclude study entry No prior chemotherapy No prior radiotherapy More than 4 weeks since prior major surgery Prior incomplete resection allowed No other prior antitumor treatment

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: Treatment<br>Patients receive bryostatin 1 IV over 72 hours on days 1-3 followed by cisplatin IV over 1 hour on day 4. Treatment repeats every 3 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity. | Drug: bryostatin 1<br>* Given IV<br>* Other names: Bryostatin;Drug: cisplatin<br>* Given IV<br>* Other names: DDP;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observed Response Rate. | All patients had measurable disease and were assessed after 2 cycles of chemotherapy by medical photograph, plain x-ray, CT, MRI or other imaging scans of at least 2.0 cm or greater with conventional techniques or 1.0 cm or greater with spiral CT. Patients were evaluated by RECIST criteria. All measurable lesions, up to 10 target lesions were recorded and measured at baseline across the longest diameter (LD). All other non-target lesions were documented as present or absent. Complete Response (CR) was defined as complete disappearance of the tumor, partial response (PR) was defined as at least a 30% decrease of the sum of the LD of the target lesions, using the baseline sum LD as the reference The observed response rate was defined as the percentage of evaluable patients whose best response is a CR or PR with associated 95% confidence interval. | Best response recorded from the start of treatment until disease progression/recurrence. Assessed every 2 cycles. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival was estimated according to the Kaplan-Meier product-limit method. | 18 months | 
| Progression-free Survival | Progression-free survival was estimated according to the Kaplan-Meier product-limit method | 18 months |