Pancreatic Cancer
Conditions
Brief summary
This study will evaluate the role of Gemcitabine and Abraxane in the treatment of resectable and borderline-resectable pancreatic cancer by giving the chemotherapy before surgery.
Detailed description
This current study proposes to conduct a prospective non-randomized open-label phase II trial using Gemcitabine and Abraxane in the neoadjuvant treatment of resectable and borderline-resectable pancreatic cancer. For patients that are low-risk resectable (based on prediction rule) the plan is to administer 2 cycles of Gemcitabine and Abraxane followed by additional systemic therapy or chemotherapy with radiation therapy (chemoRT), followed by surgical resection. For patients who are either borderline-resectable or high-risk resectable (see schema), the plan is to administer 2 cycles of Gemcitabine and Abraxane followed by chemoradiotherapy concurrent with gemcitabine followed by surgical resection. For those without high-risk features, systemic chemotherapy alone will be administered. The primary endpoints will be R0 surgical resection rate, biochemical (CA 19-9), pathologic and radiologic response rates. Secondary endpoints will include progression-free survival (PFS), overall survival (OS), 30-day post-op mortality, toxicity, quality of life, pain control, and correlative molecular exploratory analysis involving pancreatic tumor and stromal SPARC expression levels. The investigators will also assess the patient, tumor, and clinical characteristics that may predict R0 resectability, thus further refining the predictive rule in high-risk patients as defined by Bao and colleagues. The investigators' hypothesis is that by using targeted and risk-adapted chemotherapy or chemoRT, improved R0 surgical resections can be achieved and effective systemic therapy delivered, which will translate to a significant improvement in overall survival in patients with pancreatic adenocarcinoma, compared to published historical controls.
Interventions
DRUGChemotherapy
Nab-paclitaxel 100 mg/m2 IV over 30 minutes on days 1, 8, and 15 along with gemcitabine 1000 mg/m2 IV over 30 minutes on days 1, 8, and 15 in an every 28 day cycle for two cycles. Subjects with low risk disease will have an additional two cycles of therapy (4 total cycles) prior to resection.
DRUGChemotherapy + ChemoRadiotherapy
Nab-paclitaxel 100 mg/m2 IV over 30 minutes on days 1, 8, and 15 along with gemcitabine 1000 mg/m2 IV over 30 minutes on days 1, 8, and 15 in an every 28 day cycle for two cycles. Subjects with high-risk or borderline resectable disease will receive additional chemotherapy with radiation therapy prior to resection.
Sponsors
University of Florida
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* • Histologically or cytologically confirmed adenocarcinoma of the pancreas. * Patients must have locally advanced pancreatic cancer, classified as either low-risk resectable (LR), high-risk resectable (HR) or borderline resectable (BR) * Age between 18 and 90 years at the time of consent. * Patients with biliary obstruction must have adequate drainage prior to starting treatment. * Patients must have ≤ Grade I peripheral neuropathy (CTCAE v 4.0) * Patients must have ≤ ECOG Performance status 2 * Pretreatment laboratory parameters: * Absolute granulocyte/neutrophil count (AGC/ANC) ≥ 1.8 thou/mm3 * Platelet count ≥ 100,000/mm3 * Bilirubin \< 2 mg/dl * ALT/SGPT \< 10x upper limit of normal * Creatinine \< 3 mg/dl * Calculated creatinine clearance (via Cockcroft-Gault) \> 30 mL/min * Baseline CA 19-9 levels * Signed study specific, IRB stamped informed consent
Exclusion criteria
* • Evidence of any distant metastasis including peritoneal seeding and/or malignant ascites * Previous irradiation to the abdomen that would compromise the ability to deliver the prescribed treatment * Prior treatment for pancreatic cancer * Active, untreated infection * Surgical resection of the tumor (not including biopsies) * Other malignancy (except non-melanoma skin cancer) that has not been disease-free for at least 5 years. * Pregnant and/or breast-feeding women, or patients (men and women) of child-producing potential not willing to use medically acceptable contraception while on treatment and for at least 3 months thereafter. * Use of anti-epileptics (drugs such as phenytoin, phenobarbitol and carbamazepine) * ECG abnormality with the following: QTC \>500, left bundle branch block or any other clinically significant finding that would interfere with protocol therapy. * History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical Response Rate | 4 - 8 weeks after neoadjuvant therapy | Biochemical response rate (serum CA 19-9). Baseline compared to pre-operative serum CA19-9 values. |
| Radiographic Response Rate | 4 - 8 weeks after neoadjuvant therapy | Evaluate radiographic response of the measurable disease with repeat imaging at 4 - 8 weeks after therapy. Measurable disease was evaluated using Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1 criteria. Per RECIST v1.1 in target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), \>20% growth in the sum of the longest diameter or target lesions or appearance of new lesions; Stable Disease (SD), change in sum of longest diameter of target lesions does not meet criteria for PR or PD. The number of subjects experiencing Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD) is reported. |
| Pathologic Downstaging and Margin Status | At the time of surgery after neoadjuvant therapy | Pathologic stage and margin status after resection. Pathologic downstaging was determined my looking at the rate of R0 (all residual tumor removed during surgery) vs R1 (microscopic tumor present at the resection margin per pathology) resections. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 90 Day Post-operative Mortality | 90 days after surgery | Evaluate mortality in the first 90 days after surgery |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy Individuals with low risk disease will receive nab-paclitaxel 100 mg/m2 IV over 30 minutes on days 1, 8, and 15 along with gemcitabine 1000 mg/m2 IV over 30 minutes on days 1, 8, and 15 in an every 28 day cycle for two cycles. Subjects with low risk disease will have an additional two cycles of therapy (4 total cycles) prior to resection.
Chemotherapy: Nab-paclitaxel 100 mg/m2 IV over 30 minutes on days 1, 8, and 15 along with gemcitabine 1000 mg/m2 IV over 30 minutes on days 1, 8, and 15 in an every 28 day cycle for two cycles. Subjects with low risk disease will have an additional two cycles of therapy (4 total cycles) prior to resection. | 3 |
| Chemotherapy + ChemoRadiotherapy Individuals with high-risk disease or borderline resectable disease will receive nab-paclitaxel 100 mg/m2 IV over 30 minutes on days 1, 8, and 15 along with gemcitabine 1000 mg/m2 IV over 30 minutes on days 1, 8, and 15 in an every 28 day cycle for two cycles. Subjects with high-risk or borderline resectable disease will receive additional chemotherapy with radiation therapy prior to resection.
Chemotherapy + ChemoRadiotherapy: Nab-paclitaxel 100 mg/m2 IV over 30 minutes on days 1, 8, and 15 along with gemcitabine 1000 mg/m2 IV over 30 minutes on days 1, 8, and 15 in an every 28 day cycle for two cycles. Subjects with high-risk or borderline resectable disease will receive additional chemotherapy with radiation therapy prior to resection. | 7 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease progression | 0 | 2 |
Baseline characteristics
| Characteristic | Chemotherapy | Chemotherapy + ChemoRadiotherapy | Total |
|---|---|---|---|
| Age, Continuous | 69.3 years | 67.3 years | 67.9 years |
| Region of Enrollment United States | 3 participants | 7 participants | 10 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 7 / 7 |
| serious Total, serious adverse events | 0 / 3 | 3 / 7 |
Outcome results
Primary
Biochemical Response Rate
Biochemical response rate (serum CA 19-9). Baseline compared to pre-operative serum CA19-9 values.
Time frame: 4 - 8 weeks after neoadjuvant therapy
Population: The seven subjects included in this analysis had CA19-9 testing performed at baseline and again prior to surgery. Pre-operative CA19-9 testing was not performed for one subject so they were not included in this analysis nor were two subjects who were found to have progressive disease prior to completing neoadjuvant therapy.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Chemotherapy | Biochemical Response Rate | Baseline CA19-9 | 383 U/mL |
| Chemotherapy | Biochemical Response Rate | Pre-Operative CA19-9 | 43 U/mL |
| Chemotherapy + ChemoRadiotherapy | Biochemical Response Rate | Baseline CA19-9 | 550 U/mL |
| Chemotherapy + ChemoRadiotherapy | Biochemical Response Rate | Pre-Operative CA19-9 | 53 U/mL |
Primary
Pathologic Downstaging and Margin Status
Pathologic stage and margin status after resection. Pathologic downstaging was determined my looking at the rate of R0 (all residual tumor removed during surgery) vs R1 (microscopic tumor present at the resection margin per pathology) resections.
Time frame: At the time of surgery after neoadjuvant therapy
Population: Subjects who had a surgical resection of their primary tumor were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemotherapy | Pathologic Downstaging and Margin Status | R0 Resection | 3 participants |
| Chemotherapy | Pathologic Downstaging and Margin Status | R1 Resection | 0 participants |
| Chemotherapy + ChemoRadiotherapy | Pathologic Downstaging and Margin Status | R0 Resection | 3 participants |
| Chemotherapy + ChemoRadiotherapy | Pathologic Downstaging and Margin Status | R1 Resection | 2 participants |
Primary
Radiographic Response Rate
Evaluate radiographic response of the measurable disease with repeat imaging at 4 - 8 weeks after therapy. Measurable disease was evaluated using Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1 criteria. Per RECIST v1.1 in target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), \>20% growth in the sum of the longest diameter or target lesions or appearance of new lesions; Stable Disease (SD), change in sum of longest diameter of target lesions does not meet criteria for PR or PD. The number of subjects experiencing Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD) is reported.
Time frame: 4 - 8 weeks after neoadjuvant therapy
Population: All subjects enrolled in the study were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemotherapy | Radiographic Response Rate | Partial Response | 1 participants |
| Chemotherapy | Radiographic Response Rate | Stable Disease | 2 participants |
| Chemotherapy | Radiographic Response Rate | Progressive Disease | 0 participants |
| Chemotherapy + ChemoRadiotherapy | Radiographic Response Rate | Partial Response | 0 participants |
| Chemotherapy + ChemoRadiotherapy | Radiographic Response Rate | Stable Disease | 5 participants |
| Chemotherapy + ChemoRadiotherapy | Radiographic Response Rate | Progressive Disease | 2 participants |
Secondary
90 Day Post-operative Mortality
Evaluate mortality in the first 90 days after surgery
Time frame: 90 days after surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemotherapy | 90 Day Post-operative Mortality | Number of survival | 3 participants |
| Chemotherapy | 90 Day Post-operative Mortality | Number of mortality | 0 participants |
| Chemotherapy + ChemoRadiotherapy | 90 Day Post-operative Mortality | Number of mortality | 0 participants |
| Chemotherapy + ChemoRadiotherapy | 90 Day Post-operative Mortality | Number of survival | 5 participants |