Acinar Cell Adenocarcinoma of the Pancreas, Duct Cell Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer
Conditions
Brief summary
Phase II trial to study the effectiveness of combining paclitaxel and bryostatin-1 in treating patients who have locally advanced unresectable or metastatic pancreatic cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bryostatin-1 may help paclitaxel kill more cancer cells by making tumor cells more sensitive to the drug.
Detailed description
PRIMARY OBJECTIVES: I. To determine the response rates to weekly, sequential paclitaxel/ bryostatin-1 in patients with unresectable and metastatic pancreatic cancer. II. To determine the toxicity of therapy. III. To determine patient survival after therapy. IV. To determine Bryostatin-1 pharmacokinetics. OUTLINE: This is an open-label, multicenter study. Patients receive paclitaxel IV over 1 hour on day 1 followed by bryostatin 1 IV over 1 hour on day 2 of weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Interventions
DRUGpaclitaxel
Given IV
DRUGbryostatin 1
Given IV
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic proof of adenocarcinoma of the pancreas that is locally advanced and considered surgically not resectable or metastatic * Patients with or without prior treatment are eligible for treatment on protocol; prior treatment may have included one treatment course of chemo/RT and/ or one course of chemotherapy, but not two prior courses of chemotherapy; * Measurable disease * ECOG performance status of 0-1 * Ability to sign an informed consent form indicating awareness of the investigational nature of this study, in keeping with the policies of the hospital * Patients may not be receiving any other concurrent chemotherapy, immunotherapy, or radiotherapy; the most recent treatment for pancreatic cancer, within the limitations of allowed prior therapy must be 28 days or longer prior to enrollment on study * Absolute granulocytes \> 1,500/mm\^3 * Platelets \> 150,000/mm\^3 * Serum bilirubin \< 1.5 mg/dl * Serum creatinine \< 1.5 mg/dl
Exclusion criteria
* Presence of any ongoing toxic effect from prior treatment * Brain metastases * History of active angina or myocardial infarction within 6 months; history of significant ventricular arrhythmia requiring medication with antiarrhythmics; well controlled atrial fibrillation on standard management will be permitted * Pregnant or lactating women * Pre-existing neurotoxicity that is graded 3+ or greater * Serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy * Psychiatric disorders rendering patients incapable of complying with the requirements of the protocol * HIV infection * Any other medical condition or reason that, in the investigator's opinion, makes the patient unsuitable to participate in a clinical trial (for example a history of prior poor compliance with treatment)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate of at Least 30% | Up to 8 years | Number of participants with a Response rate of at least 30%. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Up to 8 years | — |
| Overall Survival | Up to 8 years | Computed using the Kaplan-Meier estimator. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Bryostatin 1 Pharmacokinetics | Week 1 | Not done-study terminated early |
Countries
United States
Participant flow
Recruitment details
A total of 19 patients were enrolled from 5 centers between March 2002 and October 2003.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Paclitaxel, Bryostatin 1) Patients receive paclitaxel IV over 1 hour on day 1 followed by bryostatin 1 IV over 1 hour on day 2 of weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
paclitaxel: Given IV
bryostatin 1: Given IV
pharmacological study: Correlative studies | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Death | 2 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Treatment (Paclitaxel, Bryostatin 1) |
|---|---|
| Age, Continuous | 56.0 years |
| Race/Ethnicity, Customized Hispanic | 3 participants |
| Race/Ethnicity, Customized Non-Hispanic black | 3 participants |
| Race/Ethnicity, Customized Non-Hispanic whites | 13 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 19 |
| serious Total, serious adverse events | 10 / 19 |
Outcome results
Primary
Response Rate of at Least 30%
Number of participants with a Response rate of at least 30%. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST).
Time frame: Up to 8 years
Population: data not met
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Paclitaxel, Bryostatin 1) | Response Rate of at Least 30% | 0 participants |
Secondary
Number of Participants With Adverse Events
Time frame: Up to 8 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Paclitaxel, Bryostatin 1) | Number of Participants With Adverse Events | 10 Participants |
Secondary
Overall Survival
Computed using the Kaplan-Meier estimator.
Time frame: Up to 8 years
Population: Patients with locally advanced or metastatic pancreatic adenocarcinoma received a total of 52 cycles of therapy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Paclitaxel, Bryostatin 1) | Overall Survival | 17 Participants |
Other Pre-specified
Bryostatin 1 Pharmacokinetics
Not done-study terminated early
Time frame: Week 1