Resectable Pancreatic Cancer, Pancreatic Ductal Carcinoma
Conditions
Keywords
Resectable pancreatic cancer, Pancreatic Ductal Carcinoma
Brief summary
This research study is a Phase II clinical trial, which evaluates a combination of drugs, FOLFIRINOX and Gemcitabine/Nab-Paclitaxel, in the management of participants with resectable pancreatic cancer prior to surgery.
Detailed description
Patients who fulfill eligibility criteria will be randomized to Arm A or Arm B * Treatment will be administered on an outpatient basis. * Upon registration participants will be randomized to Arm A (FOLFIRINOX) or Arm B (Gemcitabine/nab-Paclitaxel). * After completion of FOLFIRINOX or Gemcitabine/Nab-paclitaxel, all participants without progressive disease will proceed to radiation therapy with capecitabine . * Between 2 and 4 weeks after radiation is complete, participants will proceed for surgical resection of pancreatic cancer
Interventions
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cytologic or histologic proof of pancreatic ductal carcinoma is required prior to study entry. * No evidence of metastatic disease as determined by chest CT scan, and abdominal CT scan (or MRI with gadolinium and/or manganese) and laparoscopy. All patients must be staged with a physical exam, chest CT, abdominal CT with intravenous contrast (or abdominal MRI with gadolinium and/or manganese). Only potentially resectable patients are eligible. Potentially resectable is defined as a) no extrapancreatic disease, b) no evidence (on CT) of involvement of the celiac axis or SMA, c) no evidence (CT or MRI) of occlusion of the SMV or SMPV confluence, and d) no evidence of gross peritoneal or distant metastases by laparoscopy. * Patients must be 18 years old or older. There will be no upper age restriction. * ECOG Performance Status of 0 or 1 are eligible. * Life expectancy of greater than 3 months. * Lab Values: * ANC ≥ 1500 cells/mm3 * Platelet count at least 100,000 cells/mm3. * AST and ALT ≤2.5 x upper limit of normal * Total Bilirubin ≤ 5 x upper limit of normal if patient is s/p biliary stenting AND decreasing at least two time points after stenting. * Total Bilirubin ≤ 1.5 x upper limit of normal if no biliary stenting was done * Serum Creatinine ≤1.5mg/dl OR * Creatinine Clearance greater than or equal to 30ml/min (as estimated by Cockroft Gault Equation) (140 - age \[yrs\]) (body wt \[kg\]) * Creatinine clearance for males = ------------ (72) (serum creatinine \[mg/dL\]) * Creatinine clearance for females = 0.85 x male value * The effects of radiation on the developing human fetus are known to be teratogenic. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study treatment plus 30 days from the last date of study drug administration. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
Patients who fulfill any of the following criteria will be excluded: * The presence of metastatic disease on imaging or laparoscopy. * Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator), such as significant cardiac or pulmonary morbidity e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months, ongoing infection as manifested by fever. * Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test (serum or urine) at baseline. (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). * Any prior chemotherapy or radiation for treatment of the patient's pancreatic tumor. * Diagnosis for other invasive carcinomas (except basal cell carcinoma/squamous cell carcinoma of the skin) within the last five years. Carcinoma in-situ is allowed. * Other serious uncontrolled medical conditions that the investigator feels might compromise study participation. * Unwillingness to participate or inability to comply with the protocol for the duration of the study. * Participation in any investigational drug study within 4 weeks preceding the start of study treatment. * History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intake. * Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival Rate at 18 Month | 18 Month | Number of participants surviving after 18 months of study follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of Biomarkers With PFS | 2 Years | Analysis of the correlation between selected bio-markers and progression free survival. |
| Rate of Pathologic Downstaging | 2 Years | The number of participants achieving a reduction in the pathological staging of the primary cancer. |
| Pathologic Complete Response Rate (pCR). | 18 Months | Number of patients achieving pathologic complete response at 18 months. Pathologic complete response is defined as the absence of residual invasive disease in the panaceas and in the regional lymph nodes. |
| 30-day Post-operative Mortality Rate | 30 Days | Number of patients who died following surgery. |
| Number of Participants With Serious and Non-Serious Adverse Events | Baseline, 28 Days | Number of Participants with Serious and Non-Serious Adverse Events from baseline to 28 days |
| Surgical Morbidity Rate | within 30 days of surgery | Number of patients experiencing a specific surgery related morbidity |
| Local Control Rate | 2 Years | The number of participants achieving local control. The local control rate is defined as the number of participants achieving stable disease, partial response, or a complete response. |
| Overall Survival Rate | Baseline, 5 Years | Overall survival rate at five years using Kaplan-Meier survival analysis |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Folfirinox-ARM A Upon registration patients will be randomized to Arm A (FOLFIRINOX) or Arm B (Gemcitabine/nab-Paclitaxel
* Treatment will be administered on an outpatient basis and will include intravenous administration of the FOLFIRINOX regimen on predetermined days.
* After completion of FOLFIRINOX all patients without progressive disease will proceed with radiation therapy with the standard dose of capecitabine.
* Between 2 and 4 weeks after radiation is complete, patients will proceed for surgical resection of pancreatic cancer
FOLFIRINOX
Radiation therapy
Capecitabine | 4 |
| Gemcitabine/Nab-Paclitaxel- Arm B * Treatment will be administered on an outpatient basis. Upon registration patients will be randomized to Arm A (FOLFIRINOX) or Arm B (Gemcitabine/nab-Paclitaxel).
* Intravenous administration of the Gemcitabine/Nab-paclitaxel regimen on predetermined days of each 28 day treatment cycle (unless a delay is mandated by toxicity criteria). A cycle of Gemcitabine/Nab-paclitaxel will constitute a 28 day treatment period.
* After Gemcitabine/Nab-paclitaxel, all patients without progressive disease will proceed to radiation therapy with the standard dose of capecitabine
* Between 2 and 4 weeks after radiation is complete, patients will proceed for surgical resection of pancreatic cancer
Gemcitabine/nab-Paclitaxel
Radiation therapy
Capecitabine | 3 |
| Total | 7 |
Baseline characteristics
| Characteristic | Folfirinox-ARM A | Gemcitabine/Nab-Paclitaxel- Arm B | Total |
|---|---|---|---|
| Age, Continuous | 63.4 years | 71.9 years | 65.6 years |
| Region of Enrollment United States | 4 participants | 3 participants | 7 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 4 | 0 / 3 |
| other Total, other adverse events | 4 / 4 | 3 / 3 |
| serious Total, serious adverse events | 0 / 4 | 2 / 3 |
Outcome results
Primary
Survival Rate at 18 Month
Number of participants surviving after 18 months of study follow-up
Time frame: 18 Month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Folfirinox-ARM A | Survival Rate at 18 Month | 2 Participants |
| Gemcitabine/Nab-Paclitaxel- Arm B | Survival Rate at 18 Month | 3 Participants |
Secondary
30-day Post-operative Mortality Rate
Number of patients who died following surgery.
Time frame: 30 Days
Population: Study ended prematurely, no results available
| Arm | Measure | Value |
|---|---|---|
| Folfirinox-ARM A | 30-day Post-operative Mortality Rate | 0 |
| Gemcitabine/Nab-Paclitaxel- Arm B | 30-day Post-operative Mortality Rate | 0 |
Secondary
Correlation of Biomarkers With PFS
Analysis of the correlation between selected bio-markers and progression free survival.
Time frame: 2 Years
Population: Data not available. Study was terminated before endpoint was able to be evaluated
| Arm | Measure | Value |
|---|---|---|
| Folfirinox-ARM A | Correlation of Biomarkers With PFS | 0 |
| Gemcitabine/Nab-Paclitaxel- Arm B | Correlation of Biomarkers With PFS | 0 |
Secondary
Local Control Rate
The number of participants achieving local control. The local control rate is defined as the number of participants achieving stable disease, partial response, or a complete response.
Time frame: 2 Years
Population: Data not available. Study was terminated before endpoint was able to be evaluated
| Arm | Measure | Value |
|---|---|---|
| Folfirinox-ARM A | Local Control Rate | 0 |
| Gemcitabine/Nab-Paclitaxel- Arm B | Local Control Rate | 0 |
Secondary
Number of Participants With Serious and Non-Serious Adverse Events
Number of Participants with Serious and Non-Serious Adverse Events from baseline to 28 days
Time frame: Baseline, 28 Days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Folfirinox-ARM A | Number of Participants With Serious and Non-Serious Adverse Events | Serious Adverse Events | 0 participants |
| Folfirinox-ARM A | Number of Participants With Serious and Non-Serious Adverse Events | Other Adverse Events | 4 participants |
| Gemcitabine/Nab-Paclitaxel- Arm B | Number of Participants With Serious and Non-Serious Adverse Events | Serious Adverse Events | 2 participants |
| Gemcitabine/Nab-Paclitaxel- Arm B | Number of Participants With Serious and Non-Serious Adverse Events | Other Adverse Events | 3 participants |
Secondary
Overall Survival Rate
Overall survival rate at five years using Kaplan-Meier survival analysis
Time frame: Baseline, 5 Years
Population: Study terminated before endpoint was reached, no data available
Secondary
Pathologic Complete Response Rate (pCR).
Number of patients achieving pathologic complete response at 18 months. Pathologic complete response is defined as the absence of residual invasive disease in the panaceas and in the regional lymph nodes.
Time frame: 18 Months
Population: No Data available. Study terminated before any patients reached 18 months of follow-up. Patients were not able to be evaluated for response.
| Arm | Measure | Value |
|---|---|---|
| Folfirinox-ARM A | Pathologic Complete Response Rate (pCR). | 0 |
| Gemcitabine/Nab-Paclitaxel- Arm B | Pathologic Complete Response Rate (pCR). | 0 |
Secondary
Rate of Pathologic Downstaging
The number of participants achieving a reduction in the pathological staging of the primary cancer.
Time frame: 2 Years
Population: Data not available. Study was terminated before endpoint was able to be evaluated
| Arm | Measure | Value |
|---|---|---|
| Folfirinox-ARM A | Rate of Pathologic Downstaging | 0 |
| Gemcitabine/Nab-Paclitaxel- Arm B | Rate of Pathologic Downstaging | 0 |
Secondary
Surgical Morbidity Rate
Number of patients experiencing a specific surgery related morbidity
Time frame: within 30 days of surgery
Population: Study ended prematurely, no results available
| Arm | Measure | Value |
|---|---|---|
| Folfirinox-ARM A | Surgical Morbidity Rate | 0 |
| Gemcitabine/Nab-Paclitaxel- Arm B | Surgical Morbidity Rate | 0 |