Pancreatic Cancer
Conditions
Keywords
accelerated short course, proton beam radiation
Brief summary
A standard treatment for pancreatic cancer is radiation therapy plus chemotherapy after surgery. Radiation therapy and chemotherapy are commonly given for up to six weeks. Previous research has suggested that giving the radiation and chemotherapy for a shorter amount of time (accelerated schedule) before surgery may be better tolerated. In this research study, different schedules of proton radiation therapy will be used. Each schedule will give about the same total dose of radiation. However, the total dose will be spread out over different time periods and different numbers of sessions. The purpose is to find the shortest schedule of radiation therapy that can be given without unacceptable side effects. Proton beam radiation is being used because of its unique ability to deposit its energy directly in the tumor, resulting in less radiation to normal tissue. A new type of PET scan is also being studied to see if it can help predict the response to pre-surgery treatment.
Detailed description
* Not everyone who participates in this research study will receive the same schedule of radiation therapy. The schedule of radiation therapy will depend on the number of participants enrolled on the study and how well they have tolerated their radiation schedule. All patients will receive proton beam therapy. * Here are the proposed schedules of radiation therapy. If at any point too many subjects experience too many unacceptable side effects, no subject will be enrolled to the next level. Dose Level 1: 10 radiation sessions given Monday-Friday for two weeks. Dose Level 2: 5 radiation sessions given Monday, Wednesday and Friday in Week 1 and Tuesday and Thursday in Week 2. Dose Level 3: 5 radiation sessions given Monday, Tuesday, Thursday and Friday in Week 1 and Monday in Week 2. Dose Level 4: 5 Radiation sessions given Monday through Friday in Week 1. * In Dose Levels 2, 3 and 4, there are fewer radiation sessions, but the radiation dose given at each session is slightly higher than the dose given in each of the 10 sessions of Dose Level 1. * Capecitabine will be given orally (pill form) starting on the first day of radiation therapy and will be taken for the two weeks that the participant receives radiation therapy. * On days 1, 8 and 15 of each study cycle, the participant will be seen at the clinic for: physical examination, questions about side effects; and routine blood tests. * After the last day of study treatment there will be up to a six-week rest period before surgery is performed. * About three to six weeks after the participant has finished study treatment, the following procedures will be done: CT or MRI, physical examination; questions about side effects and blood tests.
Interventions
PROCEDUREProton Beam Radiation
Given over different schedules and duration
DRUGCapecitabine
Given orally starting on day one of radiation therapy for 2 weeks
Sponsors
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Massachusetts General Hospital
Study design
Allocation
NON_RANDOMIZED
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 of histologic proof of pancreatic ductal carcinoma * No evidence of metastatic disease * 18 years of age or older * ECOG Performance Status of 0 or 1 - Lab values as outlined in the protocol
Exclusion criteria
* Tumors in the body or tail of the pancreas * Hepatic or peritoneal metastases detected by imaging or laparoscopy prior to chemoradiation * Serious concomitant systemic disorders incompatible with the study, such as significant cardiac or pulmonary morbidity, ongoing infection as manifested by fever * Pregnant or lactating women * Life expectancy of \< 3 months * Serious, uncontrolled, concurrent infection (s) * Prior chemotherapy or radiation for treatment of the patient's pancreatic tumor * Clinically significant cardiac disease or myocardial infarction within the last 12 months * Other serious uncontrolled medical condition that the investigator feels might compromise study participation * Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome * Known, existing uncontrolled coagulopathy * Any prior fluoropyrimidine therapy * Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to a 5-fluorouracil or known DPD deficiency * Participation in any investigational drug study within 4 weeks preceding the start of the study * History of uncontrolled seizures, central nervous system disorders or psychiatric disability * Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery * Patients on cimetidine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities in the 5 Radiation Sessions in One Week Arm | 3 Weeks | The number of participants that experienced a dose limiting toxicity in the arm where radiation was administered over 5 consecutive for a total dose of 25 Gray Equivalents (GyE) (Group 4). Participants were monitored for potential Dose Limiting Toxicities (DLT) for three weeks after the start of radiation. DLTs included: 1. Any grade 3 non-hematologic or hematologic toxicity requiring a greater than 7 day interruption in therapy (excluding alopecia and nausea/vomiting not controlled by optimal supportive care or 2. Any grade 4 non-hematologic toxicity or 3. Any grade 4 neutropenia or thrombocytopenia as defined by Common Terminology Criteria for Adverse Events (CTCAE v3.0) |
| Number of Participants With Grade 3 or Greater Toxicity in Phase II | 30 days after the end of treatment, up to approximately 6 months total | Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 3). The regimen was considered to be tolerated if less than 20% of participants experienced a grade 3 or greater toxicity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Pathological Complete Response | at the time of surgery (28-42 days after start of treatment) | All patients that received surgery underwent a full pathological review of their pancreaticoduodenectomy specimen according to the American Joint Committee on Cancer (AJCC) Staging Classification, 6th. Initial gross evaluation and identification of resection margins was performed jointly by the surgeon and the pathologist. Pathological complete response will be defined as the absence of any viable tumor cells within the pathologic specimen. |
| Median Progression Free Survival | from the start of treatment until death or progression, median duration of 10.4 months | The median amount of time from the start of treatment until death or disease progression, whichever occurs first. Progressive Disease (PD): A 20% or greater increase in the sum of Longest Diameter (LD) of all target lesions, taking as reference the smallest sum LD recorded since baseline. |
| Number of Participants With Surgical Morbidity | 30 days post surgery (surgery was 28-42 days after the start of treatment) | Number of participants with pancreatic or any other anastomotic leakage within 30 days of surgery |
| 30-Day Post Operative Mortality | 30 days after the time of surgery (Surgery is 28-42 days after start of treatment) | The number of participants that died within 30 days of undergoing a pancreaticoduodenectomy. |
| Number of Participants With Treatment Related Serious Adverse Events | From the start of treatment until 30 days after the end of treatment, up to approximately 5 months | The number of participants that had treatment related serious adverse events. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 3). Adverse events were considered to be serious adverse events if they were grade 3 or greater and were considered to be possibly, probably, or definitely related to treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Proton Beam Radiation/ Capecitabine Procedure/Surgery:
Proton Beam Radiation: Given over different schedules and duration
Drug:
Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Excluded final Diagnosis | 0 | 0 | 0 | 2 |
| Overall Study | Ineligible for Resection | 2 | 1 | 1 | 7 |
Baseline characteristics
| Characteristic | Proton Beam Radiation/ Capecitabine | — |
|---|---|---|
| Age, Continuous | 65 years | — |
| CA19-9 level at baseline | 136.5 units per milliliter | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 50 Participants | — |
| Sex: Female, Male Female | 23 Participants | — |
| Sex: Female, Male Male | 27 Participants | — |
| Tumor size on CT | 2.9 Centimeters | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 41 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 41 / 41 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 2 / 41 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities in the 5 Radiation Sessions in One Week Arm
The number of participants that experienced a dose limiting toxicity in the arm where radiation was administered over 5 consecutive for a total dose of 25 Gray Equivalents (GyE) (Group 4). Participants were monitored for potential Dose Limiting Toxicities (DLT) for three weeks after the start of radiation. DLTs included: 1. Any grade 3 non-hematologic or hematologic toxicity requiring a greater than 7 day interruption in therapy (excluding alopecia and nausea/vomiting not controlled by optimal supportive care or 2. Any grade 4 non-hematologic toxicity or 3. Any grade 4 neutropenia or thrombocytopenia as defined by Common Terminology Criteria for Adverse Events (CTCAE v3.0)
Time frame: 3 Weeks
Population: The participants treated with radiation therapy at the 5 fractions over 5 consecutive days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proton Beam Radiation/ Capecitabine | Number of Participants With Dose Limiting Toxicities in the 5 Radiation Sessions in One Week Arm | 0 Participants |
Primary
Number of Participants With Grade 3 or Greater Toxicity in Phase II
Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 3). The regimen was considered to be tolerated if less than 20% of participants experienced a grade 3 or greater toxicity.
Time frame: 30 days after the end of treatment, up to approximately 6 months total
Population: Participants in the Phase II portion of the trial
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proton Beam Radiation/ Capecitabine | Number of Participants With Grade 3 or Greater Toxicity in Phase II | 2 Participants |
Secondary
30-Day Post Operative Mortality
The number of participants that died within 30 days of undergoing a pancreaticoduodenectomy.
Time frame: 30 days after the time of surgery (Surgery is 28-42 days after start of treatment)
Population: The eligible participants who underwent surgical resection. The phase I arms and Phase II group were combined together for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proton Beam Radiation/ Capecitabine | 30-Day Post Operative Mortality | 0 Participants |
Secondary
Median Progression Free Survival
The median amount of time from the start of treatment until death or disease progression, whichever occurs first. Progressive Disease (PD): A 20% or greater increase in the sum of Longest Diameter (LD) of all target lesions, taking as reference the smallest sum LD recorded since baseline.
Time frame: from the start of treatment until death or progression, median duration of 10.4 months
Population: Two participants were excluded from the analysis because of ineligible final diagnoses (cholangiocarcinoma and autoimmune pancreatitis)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Proton Beam Radiation/ Capecitabine | Median Progression Free Survival | 10.4 Months |
Secondary
Number of Participants With a Pathological Complete Response
All patients that received surgery underwent a full pathological review of their pancreaticoduodenectomy specimen according to the American Joint Committee on Cancer (AJCC) Staging Classification, 6th. Initial gross evaluation and identification of resection margins was performed jointly by the surgeon and the pathologist. Pathological complete response will be defined as the absence of any viable tumor cells within the pathologic specimen.
Time frame: at the time of surgery (28-42 days after start of treatment)
Population: The eligible participants who underwent surgical resection. The phase I arms and Phase II group were combined together for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proton Beam Radiation/ Capecitabine | Number of Participants With a Pathological Complete Response | 0 Participants |
Secondary
Number of Participants With Surgical Morbidity
Number of participants with pancreatic or any other anastomotic leakage within 30 days of surgery
Time frame: 30 days post surgery (surgery was 28-42 days after the start of treatment)
Population: The eligible participants who underwent surgical resections. The phase I arms and Phase II group were combined together for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proton Beam Radiation/ Capecitabine | Number of Participants With Surgical Morbidity | 0 Participants |
Secondary
Number of Participants With Treatment Related Serious Adverse Events
The number of participants that had treatment related serious adverse events. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 3). Adverse events were considered to be serious adverse events if they were grade 3 or greater and were considered to be possibly, probably, or definitely related to treatment.
Time frame: From the start of treatment until 30 days after the end of treatment, up to approximately 5 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proton Beam Radiation/ Capecitabine | Number of Participants With Treatment Related Serious Adverse Events | 0 Participants |
| Proton Beam Radiation/ Capecitabine Dose Level 2 | Number of Participants With Treatment Related Serious Adverse Events | 0 Participants |
| Proton Beam Radiation/ Capecitabine Dose Level 3 | Number of Participants With Treatment Related Serious Adverse Events | 0 Participants |
| Proton Beam Radiation/ Capecitabine Dose Level 4 | Number of Participants With Treatment Related Serious Adverse Events | 2 Participants |