Pancreatic Cancer
Conditions
Keywords
recurrent pancreatic cancer, stage IV pancreatic cancer, stage III pancreatic cancer, adenocarcinoma of the pancreas, stage II pancreatic cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with imatinib mesylate may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gemcitabine together with imatinib mesylate works as first-line therapy in treating patients with locally advanced or metastatic pancreatic cancer.
Detailed description
OBJECTIVES: Primary * Evaluate the time to progression in patients with locally advanced or metastatic pancreatic cancer treated with gemcitabine hydrochloride and imatinib mesylate as first-line therapy. Secondary * Assess the response rate in patients treated with this regimen. * Assess the percentage of patients treated with this regimen who survive 1 year or more. * Assess the toxicity of this regimen in these patients. * Assess the overall survival of patients treated with this regimen. OUTLINE: This is a multicenter, nonrandomized, open-label, uncontrolled study. Patients receive gemcitabine hydrochloride IV over 120 minutes on days 3 and 10 and oral imatinib mesylate on days 1-5 and 8-12. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.
Interventions
DRUGgemcitabine hydrochloride
DRUGimatinib mesylate
Sponsors
National Cancer Institute (NCI)
University of Medicine and Dentistry of New Jersey
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed pancreatic adenocarcinoma or poorly differentiated carcinoma (originating in the pancreas) * Locally advanced or metastatic disease * Not eligible for curative resection * Must have measurable or evaluable disease as defined by RECIST criteria * No CA19-9 elevation as only evidence of disease * No known brain metastases PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 125,000/mm³ * Bilirubin \< 1.5 times upper limit of normal (ULN) * AST and ALT ≤ 2.5 times ULN * Alkaline phosphatase \< 3 times ULN * Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective nonhormonal contraception * No coexisting medical condition that would preclude study compliance * No inability to ingest tablets * No active illness (e.g., active or uncontrolled infection, uncontrolled cardiac disease) that would preclude study participation * No chronic uncontrolled diarrhea and/or daily emesis * No other cancer within the past 5 years except for surgically removed noninvasive nonmelanoma skin cancer or in situ cervical cancer PRIOR CONCURRENT THERAPY: * No prior chemotherapy for metastatic disease * No prior gemcitabine * No prior imatinib mesylate * Prior surgical resection and adjuvant fluorouracil chemotherapy allowed provided there was an interval of \> 6 months between the last dose of adjuvant chemotherapy and recurrence of pancreatic cancer * Prior fluorouracil as a radiosensitizing agent allowed * At least 4 weeks since prior radiotherapy and recovered * Must have evidence of disease outside the radiation fields OR radiologically confirmed disease progression within the radiation fields after completion of radiotherapy * No concurrent therapeutic warfarin * Prophylactic warfarin ≤ 1 mg daily allowed for prophylaxis of central venous catheter thrombosis * Low molecular weight heparin or heparin allowed for anticoagulation * No concurrent chronic systemic corticosteroids * No other concurrent agents or therapies, including chemotherapy, immunotherapy, hormonal cancer therapy, radiotherapy, or cancer surgery * No other concurrent experimental medications * No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 4 years | Progression-free survival in months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 5 years | Response rate as defined by a best response of Stable Disease or better. |
| 1-year Survival Rate | 5 years | Percentage of subjects who survive up to 1 year |
| Overall Survival | 5 years | — |
Countries
United States
Participant flow
Recruitment details
The recruitment period spanned from October 2005 through July 2009. The trial was opened at a single regional cancer center and then expanded to other centers to reach accrual goals within the target period. These included hospitals in the CINJ Oncology Group and Northwestern University's Robert H. Lurie Comprehensive Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine and Imatinib imatinib mesylate: 400 mg/day, given orally Day 1-5 and 8-12 every 21 days.
gemcitabine hydrochloride: fixed dose rate infuration at 1200 mg/m2/120 minutes on Days 3 and 10 every 21 days. | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Evaluable for toxicity but not response | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Gemcitabine and Imatinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 20 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 63 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 44 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 43 |
| serious Total, serious adverse events | 6 / 43 |
Outcome results
Primary
Progression-free Survival
Progression-free survival in months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: 4 years
Population: A total of 44 patients were enrolled. One patient withdrew consent before starting treatment. One patient was determined, after initiating treatment, to have an ampullary cancer and was evaluable for toxicity but not for response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine and Imatinib | Progression-free Survival | 3.9 months |
Secondary
1-year Survival Rate
Percentage of subjects who survive up to 1 year
Time frame: 5 years
Population: A total of 44 patients were enrolled. One patient withdrew consent before starting treatment. One patient was determined, after initiating treatment, to have an ampullary cancer and was evaluable for toxicity but not for response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine and Imatinib | 1-year Survival Rate | 25.6 percentage of total evaluable subjects |
Secondary
Overall Survival
Time frame: 5 years
Population: A total of 44 patients were enrolled. One patient withdrew consent before starting treatment. One patient was determined, after initiating treatment, to have an ampullary cancer and was evaluable for toxicity but not for response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine and Imatinib | Overall Survival | 6.23 months |
Secondary
Response Rate
Response rate as defined by a best response of Stable Disease or better.
Time frame: 5 years
Population: A total of 44 patients were enrolled. One patient withdrew consent before starting treatment. One patient was determined, after initiating treatment, to have an ampullary cancer and was evaluable for toxicity but not for response. Seven subjects were not assessed for response as they discontinued therapy treatment before response was assessed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine and Imatinib | Response Rate | 48.6 percentage of total evaluable subjects |