Pancreatic Cancer
Conditions
Keywords
Borderline resectable
Brief summary
This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of a therapy to learn whether the therapy works in treating a specific cancer. "Investigational" means that the therapy is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if therapy is effective for treating different types of cancer. Proton beam radiation therapy is an FDA (U.S. Food and Drug Administration) approved radiation delivery system. Proton beam radiation therapy is known to spare surrounding normal tissues from radiation as it delivers less radiation beyond the area of the target tissues. This may reduce side effects that patients would normally experience with standard (photon) radiation therapy, which tends to include more normal tissue along with tumor target tissue. Researchers in the laboratory have discovered that there are pathways inside the cells that can lead to growth and survival of the tumor. The chemotherapy drugs FOLFIRINOX and capecitabine are targeted towards blocking the pathways that allow cancer cells to divide, and may result in the tumor shrinking in size. In this research study, the investigators are looking to determine if proton beam radiation in combination with FOLFIRINOX and capecitabine is effective in controlling the growth of your cancer.
Detailed description
For weeks 1-8, you will only be receiving FOLFIRINOX via IV infusion. The treatment plan will begin with four cycles (8 weeks) of FOLFIRINOX. Each cycle is 14 days long. You will receive FOLFIRINOX therapy on days 1, 2 and 3 of each of the four cycles. The FOLFIRINOX treatment is broken up into three different drugs. 5-FU will be administered over two hours on day one of each cycle, and then continuously with a pump for days 2 and 3. Oxaliplatin will be delivered by intravenous (infusion) over 120 minutes. Irinotecan will be given by IV for 90 minutes. All parts of this treatment will be received as an outpatient. If after 4 cycles of FOLFIRINOX therapy, your tumor has not spread, you will receive a further 4 cycles of FOLFIRINOX. If after 8 total cycles of FOLFIRINOX your cancer is clearly resectable, you will proceed to phase 2 of treatment with capecitabine and radiation therapy. You will take tablets of capecitabine by mouth for a total of 10 days (Monday through Friday) during the two weeks after your FOLFIRINOX treatment. You will be given a drug diary for capecitabine which contains instructions on how to take the drug. Short course radiation: You will receive proton radiation treatment for five days (Monday through Friday) after your FOLFIRINOX treatment, during the time of your capecitabine treatment, or photon radiation for ten days (Monday through Friday for two weeks). You will also be assessed at least once during this treatment course for any side effects you may be experiencing. You will receive study radiation treatment as an outpatient at the Francis H. Burr Proton Center or the Clark Center for Radiation Oncology at the Massachusetts General Hospital Surgery is expected to occur approximately one to four weeks after completion of capecitabine therapy. After your surgery, you may receive additional chemotherapy at the discretion of your treating physician and be followed as per standard of care.
Interventions
DRUGFOLFIRINOX
Up to Eight-14 day cycles
DRUGCapecitabine
Orally, for 10 days
RADIATIONShort Course Radiation
Five or ten days
PROCEDURESurgery
1-4 weeks after completion of capecitabine therapy
Sponsors
Massachusetts General Hospital
National Cancer Institute (NCI)
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
* Cytologic or histologic proof pancreatic ductal carcinoma * Borderline resectable * Life expectancy of at least 3 months * ECOG Performance Status ≤ 1 * Adequate organ and bone marrow function * No treatment of other invasive cancers within the last 5 years with greater than 5% risk of recurrence at the time of eligibility screening. Carcinoma in-situ and basal cell carcinoma/squamous cell carcinoma of the skin are allowed * \> 4 weeks since major surgery, excluding laparoscopy
Exclusion criteria
* Evidence of metastatic disease * Pregnant or breastfeeding * Other serious uncontrolled medical conditions * Prior chemotherapy, targeted/biologic therapy or radiation for treatment of the pancreatic tumor * Prior systemic fluoropyrimidine therapy * History of uncontrolled seizures, central nervous system disorders or psychiatric disability * Individuals on cimetidine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of R0 Resection | Post-surgery (about 4 months post baseline) | The rate of R0 resection of patients with borderline-resectable adenocarcinoma of the head of the pancreas, along with borderline-resectable and resectable adenocarcinoma of the body and tail of the pancreas. R0 resection means that following surgery, no cancer cells are seen microscopically at the resection margin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression-Free Survival | From the start of treatment until death or disease progression, median duration of follow-up of 14.7 months | The median progression free survival as measured from the start of treatment until the time of disease progression or death, whichever occurs first. Disease status was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors). Disease progression is defined as having at least a 20% increase in the sum of the longest diameter (LD) of target lesion, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
| Median Overall Survival | From the start of treatment until up to 5 years of follow-up, median duration of follow-up of 37.7 months | Median overall survival, as measured from the start of treatment until up to 5 years of follow-up. |
| Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation | From the start of treatment until the end of chemoradiation, about 4 months | Frequency of grade 3 or greater adverse events deemed related to FOLFIRINOX+short course radiation therapy. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4). |
| The Proportion of Participants With Surgery Related Adverse Events | At the time of surgery, 30 days post-surgery | The number of participants with surgery related any grade adverse events following pancreaticoduodenectomy or distal pancreatectomy after receiving preoperative FOLFIRINOX and preoperative short course radiation therapy. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4). |
| 30 Day Post-operative Mortality Rate | 30 days post surgery (about 6 months from baseline) | The number of participants that died within 30 days after undergoing pancreaticoduodenectomy or distal pancreatectomy. |
| Local Control Rates | From the start of treatment until the end of treatment with FOLFIRINOX, or until disease progression (median duration of follow-up of approximately 14 months) | The number of participants that achieved local control. Local control was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors). Local Failure is defined as progression of the primary tumor, or to the reappearance of tumor at the primary site. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJennifer Y. Wo, MD
Massachusetts General Hospital
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FOLFIRINOX + Radiation All participants will receive the FOLFIRINOX regimen, followed by capecitabine and short course radiation therapy.
FOLFIRINOX: Up to Eight-14 day cycles
Capecitabine: Orally, for 10 days
Short Course Radiation: Five or ten days
Surgery: 1-4 weeks after completion of capecitabine therapy | 48 |
| Total | 48 |
Baseline characteristics
| Characteristic | FOLFIRINOX + Radiation |
|---|---|
| Age, Continuous | 62 years |
| CA19-9 Level ≥35 U/ml (elevated) | 36 Participants |
| CA19-9 Level <35 U/ml (Normal) | 12 Participants |
| CEA Level ≥3.4 ng/ml (elevated) | 25 Participants |
| CEA Level <3.4 ng/ml (normal) | 23 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Pancreatic Tumor Site Body | 11 Participants |
| Pancreatic Tumor Site Head | 35 Participants |
| Pancreatic Tumor Site Tail | 2 Participants |
| Region of Enrollment United States | 48 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 27 Participants |
| Tumor Size | 3.75 Centimeters (cm) |
| Vessel Involvement Arterial | 7 Participants |
| Vessel Involvement Both | 12 Participants |
| Vessel Involvement None | 1 Participants |
| Vessel Involvement Venous | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 48 |
| other Total, other adverse events | 48 / 48 |
| serious Total, serious adverse events | 24 / 48 |
Outcome results
Primary
Rate of R0 Resection
The rate of R0 resection of patients with borderline-resectable adenocarcinoma of the head of the pancreas, along with borderline-resectable and resectable adenocarcinoma of the body and tail of the pancreas. R0 resection means that following surgery, no cancer cells are seen microscopically at the resection margin.
Time frame: Post-surgery (about 4 months post baseline)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Eligible - FOLFIRINOX + Radiation | Rate of R0 Resection | 31 Participants |
| Resected Participants - FOLFIRINOX + Radiation | Rate of R0 Resection | 31 Participants |
Secondary
30 Day Post-operative Mortality Rate
The number of participants that died within 30 days after undergoing pancreaticoduodenectomy or distal pancreatectomy.
Time frame: 30 days post surgery (about 6 months from baseline)
Population: The number of participants that underwent surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Eligible - FOLFIRINOX + Radiation | 30 Day Post-operative Mortality Rate | 0 Participants |
Secondary
Correlation of Mutational Analysis Biomarkers
To correlate mutational analysis biomarkers (SNaPSHOT assay) with response to treatment
Time frame: 2 years
Secondary
Local Control Rates
The number of participants that achieved local control. Local control was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors). Local Failure is defined as progression of the primary tumor, or to the reappearance of tumor at the primary site.
Time frame: From the start of treatment until the end of treatment with FOLFIRINOX, or until disease progression (median duration of follow-up of approximately 14 months)
Population: The first 5 participants treated who only received 4 cycles of FOLFIRINOX instead of 8 were not included in the analysis of local control.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Eligible - FOLFIRINOX + Radiation | Local Control Rates | 32 Participants |
Secondary
Median Overall Survival
Median overall survival, as measured from the start of treatment until the time of death.
Time frame: From the start of treatment until the time of death, median duration of follow-up of 37.7 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Eligible - FOLFIRINOX + Radiation | Median Overall Survival | 37.7 Months |
Secondary
Median Progression-Free Survival
The median progression free survival as measured from the start of treatment until the time of disease progression or death, whichever occurs first. Disease status was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors). Disease progression is defined as having at least a 20% increase in the sum of the longest diameter (LD) of target lesion, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: From the start of treatment until death or disease progression, median duration of follow-up of 14.7 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Eligible - FOLFIRINOX + Radiation | Median Progression-Free Survival | 14.7 Months |
Secondary
Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation
Frequency of grade 3 or greater adverse events deemed related to FOLFIRINOX+short course radiation therapy. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4).
Time frame: From the start of treatment until the end of chemoradiation, about 4 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Eligible - FOLFIRINOX + Radiation | Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation | Diarrhea | 5 Participants |
| All Eligible - FOLFIRINOX + Radiation | Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation | Neutropenia | 2 Participants |
| All Eligible - FOLFIRINOX + Radiation | Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation | Febrile neutropenia | 1 Participants |
| All Eligible - FOLFIRINOX + Radiation | Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation | Lymphopenia | 1 Participants |
| All Eligible - FOLFIRINOX + Radiation | Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation | Thrombocytopenia | 1 Participants |
| All Eligible - FOLFIRINOX + Radiation | Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation | Anemia | 1 Participants |
| All Eligible - FOLFIRINOX + Radiation | Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation | Elevated alkaline phosphatase | 1 Participants |
| All Eligible - FOLFIRINOX + Radiation | Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation | Elevated bilirubin | 1 Participants |
| All Eligible - FOLFIRINOX + Radiation | Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation | Elevated AST/ALT | 1 Participants |
| All Eligible - FOLFIRINOX + Radiation | Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation | Peripheral neuropathy | 2 Participants |
| All Eligible - FOLFIRINOX + Radiation | Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation | Abdominal pain | 1 Participants |
| All Eligible - FOLFIRINOX + Radiation | Preoperative Toxicity of Grade 3 or Worse Related to FOLFIRINOX and Chemoradiation | Constipation | 1 Participants |
Secondary
Quality of Life, Symptom Burden, and Mood
Patient-reported outcomes: We will use descriptive statistics to describe Quality of Life (QOL) (EORTC QLQ-C30), symptom burden (ESAS-r) and mood (HADS) for the entire study cohort.
Time frame: 2 years
Secondary
Rate of Pathologic Downstaging
To determine the rate of pathologic down-staging among participants that underwent pancreaticoduodenectomy or distal pancreatectomy. The pathologic downstaging rate is the proportion of patients with the primary tumor and nodes downstaged based on final pathology of the surgical specimen.
Time frame: Baseline, Post surgery
Secondary
The Proportion of Participants With Surgery Related Adverse Events
The number of participants with surgery related any grade adverse events following pancreaticoduodenectomy or distal pancreatectomy after receiving preoperative FOLFIRINOX and preoperative short course radiation therapy. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4).
Time frame: At the time of surgery, 30 days post-surgery
Population: The participants that underwent surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Eligible - FOLFIRINOX + Radiation | The Proportion of Participants With Surgery Related Adverse Events | 0.375 proportion of participants |
Secondary
Utilization of Health Services (Emergency Room, Hospital and Intensive Care Unit)
Summary of the number of hospitalizations, intensive care unit (ICU) stays, emergency department (ED) stays, and palliative care use for the study population.
Time frame: 2 years