Stage III Gastric Cancer, Stage IV Gastric Cancer
Conditions
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.
Interventions
DRUGbryostatin 1
Given IV
DRUGcisplatin
Given IV
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Observed Response Rate. | Best response recorded from the start of treatment until disease progression/recurrence. Assessed every 2 cycles. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 18 months | Overall survival was estimated according to the Kaplan-Meier product-limit method. |
| Progression-free Survival | 18 months | Progression-free survival was estimated according to the Kaplan-Meier product-limit method |
Countries
United States
Participant flow
Recruitment details
From October 2000 through March 2002, a total of 12 patients signed a consent form and were enrolled on this study: 2 from COH, 8 from USC and 2 from UCD. All patients received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Patients received byrostatin-1 45µg/m2/day as a 72 hour intravenous infusion followed by a 1-hour infusion of cisplatin 50 mg/m2 on day 4 immediately at the bryostatin-1 infusion, administered every three weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity.
bryostatin 1: Given IV
cisplatin: Given IV
laboratory biomarker analysis: Correlative studies | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 5 / 12 |
Outcome results
Primary
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.
Time frame: Best response recorded from the start of treatment until disease progression/recurrence. Assessed every 2 cycles.
Population: The first 15 patients accrued to an Optimal Three-Stage Phase II design. If 3 or more responses are seen then 18 additional evaluable patients will be accrued to the second stage.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Observed Response Rate. | 0 Percentage of Participants |
Secondary
Overall Survival
Overall survival was estimated according to the Kaplan-Meier product-limit method.
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment | Overall Survival | 2.7 Months |
Secondary
Progression-free Survival
Progression-free survival was estimated according to the Kaplan-Meier product-limit method
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment | Progression-free Survival | 1.2 months |