Pancreatic Cancer
Conditions
Brief summary
The goal of this study is to determine the safety and efficacy of a chemotherapy regimen known as Modified FOLFIRINOX (mFFX) alone or with the addition of Stereotactic Body Radiotherapy (SBRT). We hope to learn if this new treatment combination helps to control the disease and improve survival for patients with locally advanced pancreatic cancer.
Detailed description
Primary Objective: To determine progression free survival for mFFX +/- SBRT. Secondary Objectives: * To determine metastasis free survival following mFFX chemotherapy alone or with SBRT. * To determine the overall survival in pancreatic cancer patients treated with chemotherapy +/- SBRT. * To determine local progression-free survival in pancreatic cancer patients after chemotherapy +/- SBRT. * To evaluate acute (within 3 months of treatment) grade 2 or greater gastritis, fistula, enteritis, or ulcer and any other grade 3-4 gastrointestinal toxicity within 3 months of treatment. * To evaluate the utility of FDG-PET for treatment planning and estimation of progression free survival. * To identify new biomarkers in pancreatic cancer. * To evaluate the quality of life of patients before and after either chemotherapy or chemotherapy and SBRT.
Interventions
DRUGOxaliplatin
Oxaliplatin 85 mg/m² IV over 2 hours on Day 1 of a 14-day cycle.
DRUGIrinotecan
Irinotecan 180 mg/m² IV over 90 minutes on Day 1 of a 14-day cycle.
DRUGLeucovorin
Leucovorin 400 mg/m² IV over 2 hours on Day 1 of a 14-day cycle.
DRUG5FU
5FU 2,400 mg/m² IV over 46 to 48 hours starting on Day 1 of a 14-day cycle.
RADIATIONStereotactic Body Radiotherapy (SBRT)
Radiotherapy treatment starting about 8 weeks after modified FOLFIRINOX induction chemotherapy, administered as 5 fractions of 8 Grey (Gy) each, on 5 separate days.
Sponsors
Stanford University
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
* Histologically-confirmed adenocarcinoma of the pancreas * Determined unresectable by a pancreatic cancer surgeon or a multi-disciplinary or gastrointestinal oncology Tumor Board. * Stable or better disease on re-staging scans * Typically, tumors \< 8.0 cm in greatest axial dimension but final determination of eligibility based upon radiation normal tissue constraints * Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2 * Leukocytes (white blood cells, WBC) ≥ 3,000/mL * Absolute neutrophil count (ANC) ≥ 1,500/mL * Platelets ≥ 50,000/mL * Total bilirubin ≤ 1.5 X institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 X institutional ULN * Creatinine within normal institutional limits * Ability to understand and the willingness to sign an informed consent form * Life expectancy \> 6 months
Exclusion criteria
* Metastatic disease * Prior radiotherapy to the upper abdomen/liver. * Prior chemotherapy for pancreatic cancer, other than up to 4 cycles of modified FOLFIRINOX. * Age \< 18 years * Uncontrolled intercurrent illness including, but not limited to: * Ongoing or active infection (or infections requiring systemic antibiotic treatment) * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness/social situations that would limit compliance with study requirements. * Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, or carcinoma in situ of the cervix. Patients with a previous malignancy without evidence of disease for \> 5 years will be allowed to enter the trial. * Pregnant or lactating * Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control (hormonal or barrier method of birth control; abstinence) for duration of the study * Women who are not post-menopausal (as defined in Appendix III) and have a positive urine or serum pregnancy test or refuse to take a pregnancy test * Male subjects who are unwilling or unable to use effective contraception for duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | 38 months | Progression-free survival (PFS) means the period of time that a participant remains alive without tumor progression either locally or at a distant site in the body (metastasis). The effect of the study treatments was assessed as the median PFS of participants in the treatment groups. The outcome is reported as the median PFS with standard deviation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local Progression-free Survival (Local PFS) | 38 months | Local progression-free survival (PFS) means the period of time that a participant remains alive without recurrence or advancement of the disease at the baseline sites of the tumor (local progression). The effect of the study treatments was assessed as the median local PFS of participants in the treatment groups. The outcome is reported as the median local PFS with standard deviation. |
| Progression-free Survival (PFS) at 1 Year | 1 year | Progression-free survival (PFS) means the period of time that a participant remains alive without tumor progression either locally or at a distant site in the body (metastasis). The effect of the study treatments was assessed as the number of participants in each treatment group that remained alive without tumor progression, at 1 year after treatment. The outcome is reported as a number without dispersion. |
| Metastasis-free Survival (MFS) | 62 months | Metastasis-free survival (MFS) means the period of time that a participant remains alive without the appearance of new tumor lesions a distant site in the body (metastasis). The effect of the study treatments was assessed as the median MFS of participants in the treatment groups. The outcome is reported as the median PFS with standard deviation. |
| Overall Survival (OS) | 62 months | The effect of the study treatments was assessed as the length of time participants in each treatment group that remained alive. The outcome is reported as the median OS with standard deviation. |
| Grade 2 or Greater Gastrointestinal (GI) Toxicity | 3 months | Toxicity means an adverse event related to the study treatment. Toxicity was assessed between treatment groups as the number of treatment-related , ≥ grade 2 events of gastritis, fistula, enteritis, or ulcer; plus any other Grade 3 to 5 gastrointestinal (GI) toxicity. The outcome is reported as the number of defined adverse events by preferred term for each treatment group, occurring within 3 months of the start of treatment. These adverse events by definition are all within the Common Terminology Criteria for Adverse Events (CTCAE) version 4.01 Gastrointestinal Body System. The outcome is reported as numbers without dispersion. All-cause Mortality mFFX 7 SBRT 8 |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Modified FOLFIRINOX Modified FOLFIRINOX (mFFX), a chemotherapeutic treatment regimen of 5FU, leucovorin, irinotecan, and oxaliplatin.
* Oxaliplatin 85 mg/m² IV over 2 hours on Day 1 of a 14-day cycle.
* Irinotecan 180 mg/m² IV over 90 minutes on Day 1 of a 14-day cycle.
* Leucovorin 400 mg/m² IV over 2 hours on Day 1 of a 14-day cycle.
* 5FU: 5FU 2,400 mg/m² IV over 46 to 48 hours starting on Day 1 of a 14-day cycle. | 12 |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy Modified FOLFIRINOX (mFFX), a chemotherapeutic treatment regimen of 5FU, leucovorin, irinotecan, and oxaliplatin, in combination with stereotactic body radiotherapy (SBRT)
* Oxaliplatin 85 mg/m² IV over 2 hours on Day 1 of a 14-day cycle.
* Irinotecan 180 mg/m² IV over 90 minutes on Day 1 of a 14-day cycle.
* Leucovorin 400 mg/m² IV over 2 hours on Day 1 of a 14-day cycle.
* 5FU: 5FU 2,400 mg/m² IV over 46 to 48 hours starting on Day 1 of a 14-day cycle.
* Stereotactic Body Radiotherapy (SBRT): Radiotherapy treatment starting about 8 weeks after modified FOLFIRINOX induction chemotherapy, administered as 5 fractions of 8 Grey (Gy) each, on 5 separate days. | 13 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawn due to non-coverage by insurance | 0 | 1 |
| Overall Study | Withdrawn to receive chemotherapy | 1 | 0 |
Baseline characteristics
| Characteristic | Modified FOLFIRINOX | Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 5 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 8 Participants | 14 Participants |
| Age, Continuous | 64.1 years STANDARD_DEVIATION 8 | 62.0 years STANDARD_DEVIATION 7.3 | 63 years STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 12 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 12 Participants |
| Region of Enrollment United States | 12 participants | 13 participants | 25 participants |
| Sex: Female, Male Female | 9 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 3 Participants | 9 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 12 | 8 / 13 |
| other Total, other adverse events | 12 / 12 | 13 / 13 |
| serious Total, serious adverse events | 5 / 12 | 7 / 13 |
Outcome results
Primary
Progression-free Survival (PFS)
Progression-free survival (PFS) means the period of time that a participant remains alive without tumor progression either locally or at a distant site in the body (metastasis). The effect of the study treatments was assessed as the median PFS of participants in the treatment groups. The outcome is reported as the median PFS with standard deviation.
Time frame: 38 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Modified FOLFIRINOX | Progression-free Survival (PFS) | 6.5 months | Standard Deviation 6.6 |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Progression-free Survival (PFS) | 8.4 months | Standard Deviation 9.5 |
Secondary
Grade 2 or Greater Gastrointestinal (GI) Toxicity
Toxicity means an adverse event related to the study treatment. Toxicity was assessed between treatment groups as the number of treatment-related , ≥ grade 2 events of gastritis, fistula, enteritis, or ulcer; plus any other Grade 3 to 5 gastrointestinal (GI) toxicity. The outcome is reported as the number of defined adverse events by preferred term for each treatment group, occurring within 3 months of the start of treatment. These adverse events by definition are all within the Common Terminology Criteria for Adverse Events (CTCAE) version 4.01 Gastrointestinal Body System. The outcome is reported as numbers without dispersion. All-cause Mortality mFFX 7 SBRT 8
Time frame: 3 months
Population: Analysis group is those participants that received at least one dose of the Modified FOLFIRINOX (mFFX) chemotherapy regimen.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Duodenal perforation | 0 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Gastrointestinal bleed (hemorrhage), upper | 0 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Colitis | 1 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Gastrointestinal inflammation (enterocolitis) | 1 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Fistula, anal | 0 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Nausea | 3 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Diarrhea | 3 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Pain, abdominal | 3 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Fluid in abdomen (ascites) | 0 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Pain, intractable (due to disease progression) | 0 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Colonic obstruction | 1 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Stool discolored, clay color | 1 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Gastrointestinal bleed (hemorrhage) | 1 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Vomited blood (hematemesis) | 0 Related adverse events |
| Modified FOLFIRINOX | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Blood in stool (melena) | 1 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Vomited blood (hematemesis) | 4 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Blood in stool (melena) | 0 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Colitis | 0 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Colonic obstruction | 0 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Diarrhea | 0 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Duodenal perforation | 1 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Fistula, anal | 3 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Fluid in abdomen (ascites) | 2 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Gastrointestinal bleed (hemorrhage) | 1 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Gastrointestinal bleed (hemorrhage), upper | 3 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Gastrointestinal inflammation (enterocolitis) | 0 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Nausea | 1 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Pain, abdominal | 4 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Pain, intractable (due to disease progression) | 1 Related adverse events |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Grade 2 or Greater Gastrointestinal (GI) Toxicity | Stool discolored, clay color | 0 Related adverse events |
Secondary
Local Progression-free Survival (Local PFS)
Local progression-free survival (PFS) means the period of time that a participant remains alive without recurrence or advancement of the disease at the baseline sites of the tumor (local progression). The effect of the study treatments was assessed as the median local PFS of participants in the treatment groups. The outcome is reported as the median local PFS with standard deviation.
Time frame: 38 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Modified FOLFIRINOX | Local Progression-free Survival (Local PFS) | 6.5 months | Standard Deviation 6.6 |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Local Progression-free Survival (Local PFS) | 8.4 months | Standard Deviation 10.5 |
Secondary
Metastasis-free Survival (MFS)
Metastasis-free survival (MFS) means the period of time that a participant remains alive without the appearance of new tumor lesions a distant site in the body (metastasis). The effect of the study treatments was assessed as the median MFS of participants in the treatment groups. The outcome is reported as the median PFS with standard deviation.
Time frame: 62 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Modified FOLFIRINOX | Metastasis-free Survival (MFS) | 12.9 months | Standard Deviation 6.4 |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Metastasis-free Survival (MFS) | 10.8 months | Standard Deviation 16.9 |
Secondary
Overall Survival (OS)
The effect of the study treatments was assessed as the length of time participants in each treatment group that remained alive. The outcome is reported as the median OS with standard deviation.
Time frame: 62 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Modified FOLFIRINOX | Overall Survival (OS) | 12.9 months | Standard Deviation 6.4 |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Overall Survival (OS) | 13.4 months | Standard Deviation 16.6 |
Secondary
Progression-free Survival (PFS) at 1 Year
Progression-free survival (PFS) means the period of time that a participant remains alive without tumor progression either locally or at a distant site in the body (metastasis). The effect of the study treatments was assessed as the number of participants in each treatment group that remained alive without tumor progression, at 1 year after treatment. The outcome is reported as a number without dispersion.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Modified FOLFIRINOX | Progression-free Survival (PFS) at 1 Year | 5 Participants |
| Modified FOLFIRINOX Plus Stereotactic Body Radiotherapy | Progression-free Survival (PFS) at 1 Year | 2 Participants |