Pancreatic CancerPhase 1/2NCT00438256
Neoadjuvant Accelerated Short Course Radiation Therapy With Proton Beam and Capecitabine for Resectable Pancreatic Cancer
A Phase 1/2 study testing Proton Beam Radiation and Capecitabine in people with Pancreatic Cancer, run by Massachusetts General Hospital at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- Proton Beam Radiation and Capecitabine
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2007to Dec 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 17Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Massachusetts General Hospital
Boston, Massachusetts, 02215
About this study
Official title: Phase I/II of Neoadjuvant Accelerated Short Course Radiation Therapy With Proton Beam and Capecitabine for Resectable Pancreatic Cancer
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.
Read the 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.
- Conditions
- Pancreatic Cancer
- Being tested
- Proton Beam Radiation, Capecitabine
- Keywords
- accelerated short course, proton beam radiation
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Proton Beam RadiationProcedure or surgery
Given over different schedules and duration
CapecitabineDrug
Given orally starting on day one of radiation therapy for 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | 10 Radiation Sessions over 2 weeks Receives: Procedure: Proton Beam Radiation; Drug: Capecitabine |
| Group 2 | Experimental | 5 Radiation sessions: 3 in week 1 and 2 in week 2 Receives: Procedure: Proton Beam Radiation; Drug: Capecitabine |
| Group 3 | Experimental | 5 Radiation sessions: 4 in week 1 and 1 in week 2 Receives: Procedure: Proton Beam Radiation; Drug: Capecitabine |
| Group 4 | Experimental | 5 Radiation Sessions in one week Receives: Procedure: Proton Beam Radiation; Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- 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
- Any grade 4 non-hematologic toxicity or
- Any grade 4 neutropenia or thrombocytopenia as defined by Common Terminology Criteria for Adverse Events (CTCAE v3.0)
Measured: 3 Weeks
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.
Measured: 30 days after the end of treatment, up to approximately 6 months total
Secondary outcomes (5)
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.
Measured: at the time of surgery (28-42 days after start of treatment)
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.
Measured: from the start of treatment until death or progression, median duration of 10.4 months
Number of Participants With Surgical Morbidity
Number of participants with pancreatic or any other anastomotic leakage within 30 days of surgery
Measured: 30 days post surgery (surgery was 28-42 days after the start of treatment)
30-Day Post Operative Mortality
The number of participants that died within 30 days of undergoing a pancreaticoduodenectomy.
Measured: 30 days after the time of surgery (Surgery is 28-42 days after start of treatment)
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.
Measured: From the start of treatment until 30 days after the end of treatment, up to approximately 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2007 (estimated)
- Study startDec 2007
- Primary completionDec 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Theodore Sunki Hong, Massachusetts General Hospital
- Investigators
- Theodore Hong, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00438256
- Sponsor's protocol ID
- 06-248
- Status last verified
- Dec 2018
- First submitted
- 20 Feb 2007
- Last updated
- 23 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Hong TS, Ryan DP, Borger DR, Blaszkowsky LS, Yeap BY, Ancukiewicz M, Deshpande V, Shinagare S, Wo JY, Boucher Y, Wadlow RC, Kwak EL, Allen JN, Clark JW, Zhu AX, Ferrone CR, Mamon HJ, Adams J, Winrich B, Grillo T, Jain RK, DeLaney TF, Fernandez-del Castillo C, Duda DG. A phase 1/2 and biomarker study of preoperative short course chemoradiation with proton beam therapy and capecitabine followed by early surgery for resectable pancreatic ductal adenocarcinoma. Int J Radiat Oncol Biol Phys. 2014 Jul 15;89(4):830-8. doi: 10.1016/j.ijrobp.2014.03.034. Epub 2014 May 24.
PubMed 24867540
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II of Neoadjuvant Accelerated Short Course Radiation Therapy With Proton Beam and Capecitabine for Resectable Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT00438256
- Acronym / sponsor ID
- 06-248
- Conditions
- Pancreatic Cancer
- Keywords
- accelerated short course, proton beam radiation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, National Cancer Institute (NCI)
- Study start
- Dec 2007
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 22 Feb 2007 (estimated)
- Results
- Posted 23 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Procedure: Proton Beam Radiation, Drug: Capecitabine10 Radiation Sessions over 2 weeks |
| Group 2 | Experimental | Procedure: Proton Beam Radiation, Drug: Capecitabine5 Radiation sessions: 3 in week 1 and 2 in week 2 |
| Group 3 | Experimental | Procedure: Proton Beam Radiation, Drug: Capecitabine5 Radiation sessions: 4 in week 1 and 1 in week 2 |
| Group 4 | Experimental | Procedure: Proton Beam Radiation, Drug: Capecitabine5 Radiation Sessions in one week |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Proton Beam RadiationGiven over different schedules and duration | Procedure or surgery | Group 1, Group 2, Group 3, Group 4 |
| CapecitabineGiven orally starting on day one of radiation therapy for 2 weeks | Drug | Group 1, Group 2, Group 3, Group 4 |
Primary outcome
Number of Participants With Dose Limiting Toxicities in the 5 Radiation Sessions in One Week Arm
Time frame: 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
Time frame: 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.
5 secondary outcomes
Number of Participants With a Pathological Complete Response
Time frame: at the time of surgery (28-42 days after start of treatment)
Median Progression Free Survival
Time frame: from the start of treatment until death or progression, median duration of 10.4 months
Number of Participants With Surgical Morbidity
Time frame: 30 days post surgery (surgery was 28-42 days after the start of treatment)
30-Day Post Operative Mortality
Time frame: 30 days after the time of surgery (Surgery is 28-42 days after start of treatment)
Number of Participants With Treatment Related Serious Adverse Events
Time frame: From the start of treatment until 30 days after the end of treatment, up to approximately 5 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24867540Hong TS, Ryan DP, Borger DR, Blaszkowsky LS, Yeap BY, Ancukiewicz M, Deshpande V, Shinagare S, Wo JY, Boucher Y, Wadlow RC, Kwak EL, Allen JN, Clark JW, Zhu AX, Ferrone CR, Mamon HJ, Adams J, Winrich B, Grillo T, Jain RK, DeLaney TF, Fernandez-del Castillo C, Duda DG. A phase 1/2 and biomarker study of preoperative short course chemoradiation with proton beam therapy and capecitabine followed by early surgery for resectable pancreatic ductal adenocarcinoma. Int J Radiat Oncol Biol Phys. 2014 Jul 15;89(4):830-8. doi: 10.1016/j.ijrobp.2014.03.034. Epub 2014 May 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Theodore Hong, MD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Proton Beam Radiation and Capecitabine in people with Pancreatic Cancer, run by Massachusetts General Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicities in the 5 Radiation Sessions in One Week Arm (time frame: 3 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00438256, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2019.