Cancer of PancreasPhase 1NCT01446458
Phase I Study of Stereotactic Body Radiation Therapy and FOLFIRINOX in the Neoadjuvant Therapy of Pancreatic Cancer
A Phase 1 study testing Modified FOLFIRINOX and Stereotactic Body Radiotherapy (SBRT) in people with Cancer of Pancreas and Cancer of the Pancreas, run by Emory University at 2 sites in United States.
Trial summary
The purpose of this study is to determine whether using FOLFIRINOX chemotherapy and Stereotactic Body Radiation Therapy (SBRT) prior to surgery in patients with pancreatic cancer is safe and well tolerated. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Cancer of Pancreas, Cancer of the Pancreas, Neoplasms, Pancreatic
- What is being tested?
- Modified FOLFIRINOX and Stereotactic Body Radiotherapy (SBRT)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2011to Mar 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic or cytologic diagnosis of pancreatic adenocarcinoma.
- Radiographically resectable or borderline resectable disease as reviewed by an experienced surgical oncologist at Emory.
- Age 21 years or older.
- Not received prior chemotherapy or radiation for pancreatic cancer.
- ECOG performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.
- Adequate bone marrow function: absolute neutrophil count > 1,500/cmm, platelet count > 100,000/cmm.
- Understanding and be informed of the investigational nature of this study and must give written informed consent prior to the receiving of treatment per this protocol.
Who cannot join
- Histologies including endocrine tumors or lymphoma of the pancreas.
- A tumor which is less than 3 mm from the duodenum as measured by either CT or MRI.
- History of central nervous system (CNS) metastases.
- Liver dysfunction, including total bilirubin > 1.5 mg/dL; aspartate transaminase (AST) and alanine amino transferase (ALT) > 5 times upper limit of the institutional normal.
- Creatinine ≥ 1.5 mg/dL.
- Albumin ≤ 2.5 g/dL.
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- International Normalized Ratio (INR) ≥ 1.5 (in the absence of ongoing treatment with warfarin).
- Breast feeding.
- Serious active infection.
- Serious concurrent systemic disorders incompatible with participating in the study (at the discretion of the investigator).
- An active second primary malignancy (except in situ carcinoma of the cervix, or adequately treated basal cell carcinoma of the skin) within less than one year of enrollment into this study.
- Clinical evidence of distant metastatic disease.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
About this study
Official title: Phase I Study of Stereotactic Body Radiation Therapy and 5-Fluorouracil, Oxaliplatin and Irinotecan (FOLFIRINOX) in the Neoadjuvant Therapy of Pancreatic Cancer
The purpose of this study is to determine whether using FOLFIRINOX chemotherapy and Stereotactic Body Radiation Therapy (SBRT) prior to surgery in patients with pancreatic cancer is safe and well tolerated. This study will obtain preliminary data on the response of the cancer to this therapy by Magnetic Resonance Imaging (MRI) and by studying the cancer after it is resected surgically.
In addition, the investigators will perform biochemical studies on the tumor tissue obtained from your tissue biopsy as well as from the tumor removed by the surgeon in order to measure the effect of treatment with FOLFIRINOX and SBRT on several proteins that may be important in the behavior of pancreatic cancer cells.
The data obtained from this trial will be extremely valuable to help improve the approach to treating pancreatic cancer in the future. If you do not undergo surgery after completion of FOLFIRINOX + SBRT, the investigators will request a second biopsy of the tumor under computer tomography (CT) -guidance in order to measure the effect of treatment on your tumor.
Read the detailed description
The current standard of care for treating early stage pancreatic cancer involves surgery followed by chemotherapy and / or chemoradiotherapy using conventional fractionated external beam radiation therapy (EBRT). Despite the the incorporation of multi-modality adjuvant therapy following surgery, patients with surgically resected pancreas cancer have a high likelihood of recurrence of their cancer and/ or death from their disease. Patients with more advanced pancreatic cancers experience even worse outcomes in the face of unresectable disease or lower likelihood of achieving a negative margin resection. In these particular group of patients, chemotherapy and radiation given prior to surgery may help select patients who are more likely ultimately to benefit from a pancreaticoduodenectomy and may improve the rate of margin negative resection, factors which may influence their outcome.
Systemic chemotherapy traditionally used in the treatment of pancreatic cancer has included drugs such as gemcitabine or 5-fluorouracil (5-FU). Recently, a multi-agent chemotherapy regimen called FOLFIRINOX has shown significant efficacy in patients with advanced pancreatic cancer with improved tumor responses and improved overall outcomes with a reasonable toxicity profile.
Stereotactic body radiotherapy (SBRT) is a unique radiation technique that allows higher doses of radiation to be delivered to the cancer over a significantly shorter period of time compared to conventional radiation. SBRT's advantages over conventional radiation include: shorter duration of therapy (one to three days versus two to five weeks) as well as the ability to deliver full doses of chemotherapy. In treating patients with pancreatic cancer, SBRT has been tolerated and has been effective when compared historically to conventional radiation. SBRT has been combined with chemotherapy and has also been very well tolerated in patients with pancreatic cancer.
This study will ask whether giving chemotherapy with FOLFIRINOX followed in short sequence by radiation therapy using Stereotactic Body Radiation Therapy (SBRT) is safe and feasible. This study will also begin to ask what is the effect of this approach on the rate of margin negative resection in patients who may subsequently undergo surgery for their pancreatic cancer.
- Conditions
- Cancer of Pancreas, Cancer of the Pancreas, Neoplasms, Pancreatic, Pancreas Cancer, Pancreas Neoplasms
- Being tested
- Modified FOLFIRINOX, Stereotactic Body Radiotherapy (SBRT)
- Keywords
- Cancer of Pancreas, Cancer of the Pancreas, Neoplasms, Pancreatic, Pancreas Cancer, Pancreas Neoplasms, Entry Term Pancreatic Cancer
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modified FOLFIRINOXDrug
Also called modifiedFOLFIRINOX
Patients receive modified FOLFIRINOX Chemotherapy for 4 cycles (1 cycle = 15 days). Modified FOLFIRINOX: Oxaliplatin 85 mg/m2 intravenous infusion on day 1; Irinotecan 180 mg/m2 intravenous infusion on day 1; 5-Fluorouracil 2400 mg/m2 continuous intravenous infusion on days 1 to 3; pegylated filgrastim (neulasta) 6 mg subcutaneous injection on day 3.
Stereotactic Body Radiotherapy (SBRT)Radiation
Also called SBRT
Patients will receive Stereotactic Body Radiotherapy (SBRT) to pancreas tumor 2 weeks following chemotherapy. SBRT is given in 3 daily fractions at designated doses per treatment cohort. Starting dose level-Dose level 1: 10 Gy SBRT to primary tumor volume (PTV) / 2 Gy SBRT to the retroperitoneal margin daily for a total Gy to Gross tumor volume (GTV) of 36 Gy. There are weekly toxicity assessments for 4 weeks. This is a standard 3 + 3 design with 4 dose levels.
| Study group | Role | What they receive |
|---|---|---|
| 5-Fluorouracil, Oxaliplatin, Irinotecan | Experimental | 5-Fluorouracil, Oxaliplatin, Irinotecan are administered as a modified FOLFIRINOX regimen every 15 days. Subjects receive bi-weekly cycles of therapy on the 1st week, the 3rd week, the 5th week and finally the 7th week for a total of 4 cycles. Assessments include history and physical, laboratory tests on a weekly basis throughout the treatment period prior to and including week 8 assessment for stereotactic body radiotherapy (SBRT). Receives: Drug: Modified FOLFIRINOX; Radiation: Stereotactic Body Radiotherapy (SBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated total dose of stereotactic body radiation to patients with resectable or borderline resectable pancreas cancer following FOLFIRINOX chemotherapy
A standard 3 + 3 design will be used for evaluating the safety and tolerability of SBRT radiation doses. Any grade 3 liver, gastric, small bowel or spinal cord toxicity or any grade 4 toxicity (hematologic or other non-hematologic except for diarrhea) will be considered a dose limiting toxicity (DLT).
Each cohort will consist of 3 patients, unless 1 of the patients experiences a DLT in which case the cohort will be expanded to 6 patients. The maximum tolerated dose (MTD) will be defined as the dose level below that which results in a DLT in 2 or more of the 6 patients in a cohort.
Measured: Four weeks
Secondary outcomes (1)
Clinical and pathologic objective response rate as measured by MRI (clinical response) and histopathology and rate of complete resection (R0) (pathologic response)
The overall pathologic (complete + partial) response rate and margin negative resection rate will be estimated using all registered patients and all resected patients (via the Intention to Treat principle for effectiveness assessment).
The overall objective clinical response rate will involve MRI assessment of pancreas tumors of all registered patients with comparison of baseline (pre-treatment) MRI measurement to post-treatment MRI measurement prior to surgical resection using the Response Evaluation Criteria in Solid Tumors (RECIST). Measurements will involve all registered patients.
Measured: ten weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2011 (estimated)
- Study startNov 2011
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cancer of PancreasStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Natalyn N. Hawk, Emory University
- Investigators
- Natalyn N. Hawk, MD, PhD, Principal investigator, Emory University Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01446458
- Sponsor's protocol ID
- IRB00051215
- Other IDs
- WCI1998-11
- Status last verified
- Mar 2016
- First submitted
- 26 Sep 2011
- Last updated
- 22 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Shaib WL, Hawk N, Cassidy RJ, Chen Z, Zhang C, Brutcher E, Kooby D, Maithel SK, Sarmiento JM, Landry J, El-Rayes BF. A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458). Int J Radiat Oncol Biol Phys. 2016 Oct 1;96(2):296-303. doi: 10.1016/j.ijrobp.2016.05.010. Epub 2016 May 24.
PubMed 27475674
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Stereotactic Body Radiation Therapy and 5-Fluorouracil, Oxaliplatin and Irinotecan (FOLFIRINOX) in the Neoadjuvant Therapy of Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT01446458
- Acronym / sponsor ID
- IRB00051215
- Conditions
- Cancer of Pancreas, Cancer of the Pancreas, Neoplasms, Pancreatic, Pancreas Cancer, Pancreas Neoplasms
- Keywords
- Cancer of Pancreas, Cancer of the Pancreas, Neoplasms, Pancreatic, Pancreas Cancer, Pancreas Neoplasms, Entry Term Pancreatic Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 5 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether using FOLFIRINOX chemotherapy and Stereotactic Body Radiation Therapy (SBRT) prior to surgery in patients with pancreatic cancer is safe and well tolerated. This study will obtain preliminary data on the response of the cancer to this therapy by Magnetic Resonance Imaging (MRI) and by studying the cancer after it is resected surgically.
In addition, the investigators will perform biochemical studies on the tumor tissue obtained from your tissue biopsy as well as from the tumor removed by the surgeon in order to measure the effect of treatment with FOLFIRINOX and SBRT on several proteins that may be important in the behavior of pancreatic cancer cells.
The data obtained from this trial will be extremely valuable to help improve the approach to treating pancreatic cancer in the future. If you do not undergo surgery after completion of FOLFIRINOX + SBRT, the investigators will request a second biopsy of the tumor under computer tomography (CT) -guidance in order to measure the effect of treatment on your tumor.
Detailed description
The current standard of care for treating early stage pancreatic cancer involves surgery followed by chemotherapy and / or chemoradiotherapy using conventional fractionated external beam radiation therapy (EBRT). Despite the the incorporation of multi-modality adjuvant therapy following surgery, patients with surgically resected pancreas cancer have a high likelihood of recurrence of their cancer and/ or death from their disease. Patients with more advanced pancreatic cancers experience even worse outcomes in the face of unresectable disease or lower likelihood of achieving a negative margin resection. In these particular group of patients, chemotherapy and radiation given prior to surgery may help select patients who are more likely ultimately to benefit from a pancreaticoduodenectomy and may improve the rate of margin negative resection, factors which may influence their outcome.
Systemic chemotherapy traditionally used in the treatment of pancreatic cancer has included drugs such as gemcitabine or 5-fluorouracil (5-FU). Recently, a multi-agent chemotherapy regimen called FOLFIRINOX has shown significant efficacy in patients with advanced pancreatic cancer with improved tumor responses and improved overall outcomes with a reasonable toxicity profile.
Stereotactic body radiotherapy (SBRT) is a unique radiation technique that allows higher doses of radiation to be delivered to the cancer over a significantly shorter period of time compared to conventional radiation. SBRT's advantages over conventional radiation include: shorter duration of therapy (one to three days versus two to five weeks) as well as the ability to deliver full doses of chemotherapy. In treating patients with pancreatic cancer, SBRT has been tolerated and has been effective when compared historically to conventional radiation. SBRT has been combined with chemotherapy and has also been very well tolerated in patients with pancreatic cancer.
This study will ask whether giving chemotherapy with FOLFIRINOX followed in short sequence by radiation therapy using Stereotactic Body Radiation Therapy (SBRT) is safe and feasible. This study will also begin to ask what is the effect of this approach on the rate of margin negative resection in patients who may subsequently undergo surgery for their pancreatic cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 5-Fluorouracil, Oxaliplatin, Irinotecan | Experimental | Drug: Modified FOLFIRINOX, Radiation: Stereotactic Body Radiotherapy (SBRT)5-Fluorouracil, Oxaliplatin, Irinotecan are administered as a modified FOLFIRINOX regimen every 15 days. Subjects receive bi-weekly cycles of therapy on the 1st week, the 3rd week, the 5th week and finally the 7th week for a total of 4 cycles. Assessments include history and physical, laboratory tests on a weekly basis throughout the treatment period prior to and including week 8 assessment for stereotactic body radiotherapy (SBRT). |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histologic or cytologic diagnosis of pancreatic adenocarcinoma.
- Radiographically resectable or borderline resectable disease as reviewed by an experienced surgical oncologist at Emory.
- Age 21 years or older.
- Not received prior chemotherapy or radiation for pancreatic cancer.
- ECOG performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.
Key exclusion criteria (12 listed)
- Histologies including endocrine tumors or lymphoma of the pancreas.
- A tumor which is less than 3 mm from the duodenum as measured by either CT or MRI.
- History of central nervous system (CNS) metastases.
- Liver dysfunction, including total bilirubin > 1.5 mg/dL; aspartate transaminase (AST) and alanine amino transferase (ALT) > 5 times upper limit of the institutional normal.
- Creatinine ≥ 1.5 mg/dL.
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 |
|---|---|---|
| Modified FOLFIRINOXAlso: modifiedFOLFIRINOXPatients receive modified FOLFIRINOX Chemotherapy for 4 cycles (1 cycle = 15 days). Modified FOLFIRINOX: Oxaliplatin 85 mg/m2 intravenous infusion on day 1; Irinotecan 180 mg/m2 intravenous infusion on day 1; 5-Fluorouracil 2400 mg/m2 continuous intravenous infusion on days 1 to 3; pegylated filgrastim (neulasta) 6 mg subcutaneous injection on day 3. | Drug | 5-Fluorouracil, Oxaliplatin, Irinotecan |
| Stereotactic Body Radiotherapy (SBRT)Also: SBRTPatients will receive Stereotactic Body Radiotherapy (SBRT) to pancreas tumor 2 weeks following chemotherapy. SBRT is given in 3 daily fractions at designated doses per treatment cohort. Starting dose level-Dose level 1: 10 Gy SBRT to primary tumor volume (PTV) / 2 Gy SBRT to the retroperitoneal margin daily for a total Gy to Gross tumor volume (GTV) of 36 Gy. There are weekly toxicity assessments for 4 weeks. This is a standard 3 + 3 design with 4 dose levels. | Radiation | 5-Fluorouracil, Oxaliplatin, Irinotecan |
Primary outcome
Maximum tolerated total dose of stereotactic body radiation to patients with resectable or borderline resectable pancreas cancer following FOLFIRINOX chemotherapy
Time frame: Four weeks
A standard 3 + 3 design will be used for evaluating the safety and tolerability of SBRT radiation doses. Any grade 3 liver, gastric, small bowel or spinal cord toxicity or any grade 4 toxicity (hematologic or other non-hematologic except for diarrhea) will be considered a dose limiting toxicity (DLT). Each cohort will consist of 3 patients, unless 1 of the patients experiences a DLT in which case the cohort will be expanded to 6 patients. The maximum tolerated dose (MTD) will be defined as the dose level below that which results in a DLT in 2 or more of the 6 patients in a cohort.
1 secondary outcome
Clinical and pathologic objective response rate as measured by MRI (clinical response) and histopathology and rate of complete resection (R0) (pathologic response)
Time frame: ten weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2016.
- Derived from this study: PubMed 27475674Shaib WL, Hawk N, Cassidy RJ, Chen Z, Zhang C, Brutcher E, Kooby D, Maithel SK, Sarmiento JM, Landry J, El-Rayes BF. A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458). Int J Radiat Oncol Biol Phys. 2016 Oct 1;96(2):296-303. doi: 10.1016/j.ijrobp.2016.05.010. Epub 2016 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.
Natalyn N. Hawk, MD, PhD principal investigator
Emory University Winship Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Modified FOLFIRINOX and Stereotactic Body Radiotherapy (SBRT) in people with Cancer of Pancreas and Cancer of the Pancreas, run by Emory University 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 7 inclusion and 12 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 22 Mar 2016. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated total dose of stereotactic body radiation to patients with resectable or borderline resectable pancreas cancer following FOLFIRINOX chemotherapy (time frame: Four weeks). 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 NCT01446458, 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 22 Mar 2016; AzTrials last refreshed its copy on 8 Nov 2026.