Pancreatic CancerPhase 2NCT03099265
Neoadjuvant Modified FOLFIRINOX and Stereotactic Body Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma
A Phase 2 study testing neoadjuvant mFOLFIRINOX and Stereotactic body radiotherapy (SBRT) in people with Pancreatic Cancer, run by Yale University at 1 site in United States.
Trial summary
Surgical resection is the only potentially curative treatment for patients with pancreatic cancer. Patients with BRPC have tumors in close contact with the vasculature but not to the extent that resection is prohibited. 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?
- neoadjuvant mFOLFIRINOX and Stereotactic body radiotherapy (SBRT)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jun 2017to 18 Sep 2019
- Phase
- Phase 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
- Histologically confirmed pancreatic adenocarcinoma
- Borderline resectable pancreatic adenocarcinoma, determined centrally by review of a diagnostic CT scan and/or MRI scan with contrast by a dedicated surgical oncologist and radiologist, or as determined by EUS, and defined according to the NCCN consensus guidelines
- ECOG Performance Status of 0-1
- Age > 18
- Laboratory parameters as follows:
- Absolute neutrophil count >=1,500/uL
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- Platelet count >=100,000/uL
- Hemoglobin >=9 g/dL
- Creatinine <1.5 X ULN or estimated GFR >30 ml/min
- Bilirubin =<1.5 X ULN
- AST and ALT =<3 X ULN
- Negative pregnancy test in women of childbearing potential
- Able to have fiducials placed in the pancreas
- Patients who received chemotherapy >5 years ago for malignancies other than pancreatic cancer are eligible
Who cannot join
- Evidence of extrapancreatic disease on diagnostic imaging (CT, MRI, or PET scan), or laparoscopy, including nodal involvement beyond the peripancreatic tissues and/or distant metastases
- Evidence of invasion into the duodenum or stomach, as determined by EGD/EUS
- Prior treatment (chemotherapy, biological therapy, or radiotherapy) for pancreatic cancer
- Prior treatment with oxaliplatin, irinotecan, fluoruouracil or capecitabine
- Major surgery within 4 weeks of study entry
- Other concurrent anticancer therapies
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- Other malignancy within the past five years (exceptions include basal cell carcinoma of the skin, cervical carcinoma in situ, and non-metastatic prostate cancer)
- Evidence of second malignancy at the time of study entry
- Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
- Grade 2 or greater sensory peripheral neuropathy
- Uncontrolled seizure disorder, active neurological disease, or known CNS disease
- Significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment
- Pregnant or nursing
- Other medical condition or reason that, in the opinion of the investigator, would preclude study participation
Trial locations and contacts
1 site in 1 country.
United States1 site
Smilow Cancer Hospital
New Haven, Connecticut, 06510
About this study
Official title: Phase II Study to Evaluate Neoadjuvant Modified FOLFIRINOX and Stereotactic Body Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma
Surgical resection is the only potentially curative treatment for patients with pancreatic cancer. Patients with BRPC have tumors in close contact with the vasculature but not to the extent that resection is prohibited. Nonetheless, retrospective studies have shown that immediate resection in these patients is associated with an increased risk of positive margins, and a margin positive resection does not improve survival over that of patients with unresectable disease. Moreover, even in those patients where a successful resection is achieved, there is a high rate of early metastatic progression suggesting that micrometastatic disease is often present at diagnosis. Therefore neoadjuvant therapy is likely to improve outcomes in patients with BRPC to increase the likelihood of achieving a margin negative resection, provide early control of occult micrometastatic disease, and select those patients without systemic progression who would benefit from surgical resection.
Read the detailed description
Given the superior outcomes with FOLFIRINOX and the potential for improved local response with SBRT, the investigators propose to evaluate the efficacy of pre-operative modified FOLFIRINOX followed by SBRT in patients with borderline resectable pancreatic adenocarcinoma. The investigators hypothesize that pre-operative modified FOLFIRINOX followed by SBRT will improve the rate of R0 resections compared to historical controls treated with standard gemcitabine-based chemotherapy and fractionated radiation prior to surgery.
- Conditions
- Pancreatic Cancer
- Being tested
- neoadjuvant mFOLFIRINOX, Stereotactic body radiotherapy (SBRT)
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
neoadjuvant mFOLFIRINOXDrug
Also called Oxaliplatin, Irinotecan, Leucovorin, 5-fluorouracil
Patients will receive 8 cycles of mFOLFIRINOX every 2 weeks. mFOLFIRINOX will be dosed as follows: Oxaliplatin 85 mg/m2, followed by folinic acid 400 mg/m2 infused over 120 minutes and irinotecan 135 mg/m2 infused over 90 minutes, followed by 5-fluorouracil 300 mg/m2 IV bolus, followed by 2,400 mg/m2 continuous infusion for 46 hours. Levoleucovorin may be substituted for folinic acid at a dose of 200 mg/m2 infused over 120 minutes.
Stereotactic body radiotherapy (SBRT)Drug
Stereotactic body radiotherapy (SBRT) will be delivered to the primary tumor and any adjacent involved nodes to 33 Gy in 5 fractions over the course of 2 weeks, and within 4 weeks of chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| patients with borderline resectable pancreatic adenocarcinoma | Experimental | Borderline resectable disease will be defined by NCCN criteria, and determined centrally by review of a diagnostic pancreas protocol CT scan and/or MRI scan with contrast by a dedicated surgical oncologist and radiologist. Receives: Drug: neoadjuvant mFOLFIRINOX; Drug: Stereotactic body radiotherapy (SBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With and Without R0 Resection
The primary outcome of this study is the R0 resection count of patients with BRPC treated with neoadjuvant mFOLFIRINOX and SBRT. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed. When the study results were entered, rate was replaced with count as the manner in which these data were summarized.
Measured: Up to 40 weeks
Secondary outcomes (6)
Number of Participants Response to Neoadjuvant Therapy Using RECIST
Response to treatment will be assessed by the treating physicians and investigators according to RECIST version 1.1. Counts of participants' RECIST category at their final visit up to 40 weeks below are provided. Per Response Evaluation Criteria In Solid TumorsCriteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response(CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Up to 40 weeks
Number of Participants With and Without Pathologic Response to Neoadjuvant Therapy
A pathologic complete response is defined as the absence of residual invasive disease at the completion of the neoadjuvant treatment. This was performed only in those that had R0 resection performed.
Measured: Up to 40 weeks
Number of Participants With and Without Recurrence
Number of participants with and without recurrence following surgery. This outcome was updated when the results were entered.
Measured: Up to 40 weeks
Number of Participants: Progression Free Survival
Presented are count of patients that had experienced either progression free survival or disease progression through the follow up period.
Measured: Up to 2 years
Number of Participants: Overall Survival
Presented are counts of patients that we either deceased or not deceased at the end of the follow up period.
Measured: Up to 2 years
Grade 3 or Greater Acute and Late Gastrointestinal Toxicity
To determine rates of grade 3 or greater gastrointestinal toxicity, including acute toxicities occurring within 3 months of treatment, and late toxicities occurring over 3 months after completion of radiation. This outcome was clarified when results were entered. The number of patients that experienced at least 1 grade 3 (or greater) event are presented.
Measured: Up to 40 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2017
- Study start26 Jun 2017
- Primary completion18 Sep 2019
- Study completion18 Sep 2019
Why it stopped: Paused due to COVID. A determination was made to stop the study because it would be impossible to reach the 65% resection rate as outlined in the protocol.
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.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Yale 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kimberly Johung, MD, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03099265
- Sponsor's protocol ID
- 2000020432
- Status last verified
- Sep 2022
- First submitted
- 28 Mar 2017
- Last updated
- 27 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study to Evaluate Neoadjuvant Modified FOLFIRINOX and Stereotactic Body Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma
- ClinicalTrials.gov ID
- NCT03099265
- Acronym / sponsor ID
- 2000020432
- Conditions
- Pancreatic Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Paused due to COVID. A determination was made to stop the study because it would be impossible to reach the 65% resection rate as outlined in the protocol.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 26 Jun 2017 (actual)
- Primary completion
- 18 Sep 2019 (actual)
- Study completion
- 18 Sep 2019 (actual)
- First posted
- 4 Apr 2017 (actual)
- Results
- Posted 27 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Surgical resection is the only potentially curative treatment for patients with pancreatic cancer. Patients with BRPC have tumors in close contact with the vasculature but not to the extent that resection is prohibited. Nonetheless, retrospective studies have shown that immediate resection in these patients is associated with an increased risk of positive margins, and a margin positive resection does not improve survival over that of patients with unresectable disease. Moreover, even in those patients where a successful resection is achieved, there is a high rate of early metastatic progression suggesting that micrometastatic disease is often present at diagnosis. Therefore neoadjuvant therapy is likely to improve outcomes in patients with BRPC to increase the likelihood of achieving a margin negative resection, provide early control of occult micrometastatic disease, and select those patients without systemic progression who would benefit from surgical resection.
Detailed description
Given the superior outcomes with FOLFIRINOX and the potential for improved local response with SBRT, the investigators propose to evaluate the efficacy of pre-operative modified FOLFIRINOX followed by SBRT in patients with borderline resectable pancreatic adenocarcinoma. The investigators hypothesize that pre-operative modified FOLFIRINOX followed by SBRT will improve the rate of R0 resections compared to historical controls treated with standard gemcitabine-based chemotherapy and fractionated radiation prior to surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| patients with borderline resectable pancreatic adenocarcinoma | Experimental | Drug: neoadjuvant mFOLFIRINOX, Drug: Stereotactic body radiotherapy (SBRT)Borderline resectable disease will be defined by NCCN criteria, and determined centrally by review of a diagnostic pancreas protocol CT scan and/or MRI scan with contrast by a dedicated surgical oncologist and radiologist. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histologically confirmed pancreatic adenocarcinoma
- Borderline resectable pancreatic adenocarcinoma, determined centrally by review of a diagnostic CT scan and/or MRI scan with contrast by a dedicated surgical oncologist and radiologist, or as determined by EUS, and defined according to the NCCN consensus guidelines
- ECOG Performance Status of 0-1
- Age > 18
- Laboratory parameters as follows:
Key exclusion criteria (14 listed)
- Evidence of extrapancreatic disease on diagnostic imaging (CT, MRI, or PET scan), or laparoscopy, including nodal involvement beyond the peripancreatic tissues and/or distant metastases
- Evidence of invasion into the duodenum or stomach, as determined by EGD/EUS
- Prior treatment (chemotherapy, biological therapy, or radiotherapy) for pancreatic cancer
- Prior treatment with oxaliplatin, irinotecan, fluoruouracil or capecitabine
- Major surgery within 4 weeks of study entry
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 |
|---|---|---|
| neoadjuvant mFOLFIRINOXAlso: Oxaliplatin, Irinotecan, Leucovorin, 5-fluorouracilPatients will receive 8 cycles of mFOLFIRINOX every 2 weeks. mFOLFIRINOX will be dosed as follows: Oxaliplatin 85 mg/m2, followed by folinic acid 400 mg/m2 infused over 120 minutes and irinotecan 135 mg/m2 infused over 90 minutes, followed by 5-fluorouracil 300 mg/m2 IV bolus, followed by 2,400 mg/m2 continuous infusion for 46 hours. Levoleucovorin may be substituted for folinic acid at a dose of 200 mg/m2 infused over 120 minutes. | Drug | patients with borderline resectable pancreatic adenocarcinoma |
| Stereotactic body radiotherapy (SBRT)Stereotactic body radiotherapy (SBRT) will be delivered to the primary tumor and any adjacent involved nodes to 33 Gy in 5 fractions over the course of 2 weeks, and within 4 weeks of chemotherapy. | Drug | patients with borderline resectable pancreatic adenocarcinoma |
Primary outcome
Number of Participants With and Without R0 Resection
Time frame: Up to 40 weeks
The primary outcome of this study is the R0 resection count of patients with BRPC treated with neoadjuvant mFOLFIRINOX and SBRT. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed. When the study results were entered, rate was replaced with count as the manner in which these data were summarized.
6 secondary outcomes
Number of Participants Response to Neoadjuvant Therapy Using RECIST
Time frame: Up to 40 weeks
Number of Participants With and Without Pathologic Response to Neoadjuvant Therapy
Time frame: Up to 40 weeks
Number of Participants With and Without Recurrence
Time frame: Up to 40 weeks
Number of Participants: Progression Free Survival
Time frame: Up to 2 years
Number of Participants: Overall Survival
Time frame: Up to 2 years
Grade 3 or Greater Acute and Late Gastrointestinal Toxicity
Time frame: Up to 40 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Kimberly Johung, MD, PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing neoadjuvant mFOLFIRINOX and Stereotactic body radiotherapy (SBRT) in people with Pancreatic Cancer, run by Yale University at 1 site 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 14 inclusion and 14 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: stopped early, as of the sponsor's last update on 27 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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 27 Oct 2022). 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 and Without R0 Resection (time frame: Up to 40 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Oct 2022.