Pancreatic Cancer, Pancreatic Neoplasms
Conditions
Keywords
Pancreatic Neoplasms, Pancreatic cancer
Brief summary
The purpose of this study is to investigate if the investigators can use a specific marker in the pancreatic tumor itself to determine which patients will benefit from receiving combination chemotherapy of gemcitabine and cisplatin after undergoing resection of a pancreatic cancer. The investigators will also investigate if there is any benefit to receiving both chemotherapy drugs as opposed to only gemcitabine after undergoing complete resection of the tumor.
Detailed description
The study will specifically be looking at ERCC1 expression in pancreas cancer with regards to its prognostic and predictive value as a biomarker for patients receiving Gem / Cis as adjuvant therapy after resection.
Interventions
DRUGGemcitabine
Standard of care chemotherapy and dosage Dose - 1000 mg/m² Schedule - Days 1 and 15; Q 28 days
DRUGCisplatin
Dose - 50 mg/m² Schedule - Days 1 and 15; Q 28 days
Sponsors
Emory University
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
1. Adults (≥ 18 years) at the time of signing informed consent form 2. Understand and voluntarily sign informed consent form 3. Able to adhere to study visit schedule and other protocol requirements 4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 5. Absolute neutrophil count ≥ 1500 / mm³ 6. Platelet count ≥ 100,000 / mm³ 7. Resectable pancreatic adenocarcinoma 8. Pathologic diagnosis of pancreatic adenocarcinoma
Exclusion criteria
1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing informed consent form 2. A history of renal dysfunction (serum creatinine \> 1.8 mg/dL) 3. Presence of active infection 4. Untreated second malignancy 5. Pregnant or breast feeding females (A urine pregnancy test will be obtained in all women of child-bearing age at initial screening prior to study enrollment and administration of chemotherapy.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence-free Survival as Measured by CT Scan | Every 3 months and then every 6 months for 2 more years after resection | Clinical data were prospectively collected. Staging was performed using 7th American Committee on Cancer criteria. Patients were followed by radiologic evaluation (CT or MRI) and carbohydrate antigen 19-9 (CA19-9) every 3 months for the first 3 years after resection to assess for recurrence. Subsequently, patients underwent imaging every 6 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunohistochemistry to Determine Status of Excision Repair Cross Complementation Gene-1 (ERCC1) Expression | At the time of resection | To determine the level of ERCC1 expression, formalin-fixed, resected tumors were stained with anti-ERCC1 monoclonal antibody (clone 8F1; Neomarkers, Fremont, CA, USA) using the Dako Autostainer (Ft. Collins, CO). The percentage and intensity of fine granular nuclear staining were graded by a single pathologist. Percentage of staining was categorized into the following groups: 0 ≤ 1%; 1 = 1-10%; 2 = 11-50%; 3 = 51-100%. Staining intensity was scored as follows: 0 = none; 1 = weak; 2 = moderate; 3 = strong. Subsequently, an overall score to dichotomize the expression level to low or high was calculated: \[(1+intensity score)/3\]\*percentage score. An overall score ≤ 2 was considered low ERCC1 expression, and \> 2 was high ERCC1 expression. |
Countries
United States
Participant flow
Recruitment details
Patients who underwent resection of a pancreatic adenocarcinoma (PDAC) were enrolled postoperatively at Winship Cancer Institute of Emory University from 2010-2013.
Pre-assignment details
Twenty-five patients were initially enrolled. Three patients were thereafter excluded; two were diagnosed with secondary malignancies (primary lung adenocarcinoma and thyroid cancer), and one had a diagnosis of cholangiocarcinoma on final surgical pathology.
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine / Cisplatin Single arm study. All patients will receive gemcitabine and cisplatin as adjuvant therapy.
Gemcitabine: Standard of care chemotherapy and dosage
Dose - 1000 mg/m²
Schedule - Days 1 and 15; Q 28 days
Cisplatin: Dose - 50 mg/m²
Schedule - Days 1 and 15; Q 28 days | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Gemcitabine / Cisplatin |
|---|---|
| Age, Continuous | 60.0 years STANDARD_DEVIATION 9.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 22 |
| serious Total, serious adverse events | 2 / 22 |
Outcome results
Primary
Recurrence-free Survival as Measured by CT Scan
Clinical data were prospectively collected. Staging was performed using 7th American Committee on Cancer criteria. Patients were followed by radiologic evaluation (CT or MRI) and carbohydrate antigen 19-9 (CA19-9) every 3 months for the first 3 years after resection to assess for recurrence. Subsequently, patients underwent imaging every 6 months.
Time frame: Every 3 months and then every 6 months for 2 more years after resection
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine / Cisplatin | Recurrence-free Survival as Measured by CT Scan | 16.7 months |
Secondary
Immunohistochemistry to Determine Status of Excision Repair Cross Complementation Gene-1 (ERCC1) Expression
To determine the level of ERCC1 expression, formalin-fixed, resected tumors were stained with anti-ERCC1 monoclonal antibody (clone 8F1; Neomarkers, Fremont, CA, USA) using the Dako Autostainer (Ft. Collins, CO). The percentage and intensity of fine granular nuclear staining were graded by a single pathologist. Percentage of staining was categorized into the following groups: 0 ≤ 1%; 1 = 1-10%; 2 = 11-50%; 3 = 51-100%. Staining intensity was scored as follows: 0 = none; 1 = weak; 2 = moderate; 3 = strong. Subsequently, an overall score to dichotomize the expression level to low or high was calculated: \[(1+intensity score)/3\]\*percentage score. An overall score ≤ 2 was considered low ERCC1 expression, and \> 2 was high ERCC1 expression.
Time frame: At the time of resection
Population: Twenty patients had tissue available for ERCC1 analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcitabine / Cisplatin | Immunohistochemistry to Determine Status of Excision Repair Cross Complementation Gene-1 (ERCC1) Expression | Low Tumor ERCC1 Expression | 15 patients |
| Gemcitabine / Cisplatin | Immunohistochemistry to Determine Status of Excision Repair Cross Complementation Gene-1 (ERCC1) Expression | High Tumor ERCC1 Expression | 5 patients |