Pancreatic CancerPhase 2NCT01661088
A Study of Neoadjuvant FOLFIRINOX and FDR-Gemcitabine With Concurrent IMRT in Patients
A Phase 2 study testing FOLFIRINOX, Intensity-modulated radiotherapy (IMRT) and Surgical Exploration in people with Pancreatic Cancer, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
The investigators hypothesize that the combination of the FOLFIRINOX regimen (a combination of 5-fluorouracil, irinotecan and oxaliplatin chemotherapy) to provide maximal systemic disease control and FDR-gemcitabine chemotherapy with concurrent IMRT (Radiation therapy) to address local disease, will achieve a… 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?
- FOLFIRINOX, Intensity-modulated radiotherapy (IMRT) and Surgical Exploration
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2011to 30 Aug 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
- Patients must have cytologic or histologic confirmation of carcinoma arising in the pancreas.
- Patients must be deemed to have borderline resectable disease with no radiologic evidence of distant metastatic disease prior to registration.
- Specifically, patients must have at least one designation of borderline resectable and no designation of unresectable disease.
- Patients must have a life expectancy of at least 12 weeks, a Zubrod performance status of < 1 and be willing and medically able to undergo surgical resection.
- Patients must have adequate organ function defined as follows: absolute neutrophil count of > 1500/mm3, platelets > 100,000/mm3, serum Cr < 1.5 mg/dl, total bilirubin < 2.0 mg/dl with relief of biliary obstruction if present (PTC tube or endobiliary stent).
- Patients must be free of other active systemic malignancy, ongoing infection, or any other serious uncontrolled, concomitant systemic disorders or psychiatric condition that would interfere with the safe delivery of protocol therapy.
- Patients of reproductive potential must agree to use an effective contraceptive method during participation in this trial due to the unacceptable teratogenic toxicity of abdominal radiation and cytotoxic chemotherapy.
- Patients must be aware of the investigational nature of the therapy and provide written informed consent.
Who cannot join
- Patients with neuroendocrine tumors are excluded.
- Active systemic malignancy, ongoing infection, or any other serious uncontrolled, concomitant systemic disorders or psychiatric condition that would interfere with the safe delivery of protocol therapy.
- Patients with preexisting peripheral neuropathy > grade 2 are ineligible
- Pregnant or nursing women are ineligible.
- Patients must have no history of previous chemotherapy for pancreatic cancer or any abdominal radiation therapy.
- Patients may not have used any investigational agent within 4 weeks prior to enrollment into the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
About this study
Official title: A Phase II Study of Neoadjuvant FOLFIRINOX and FDR-Gemcitabine With Concurrent IMRT in Patients With Borderline Resectable Pancreatic Cancer
The investigators hypothesize that the combination of the FOLFIRINOX regimen (a combination of 5-fluorouracil, irinotecan and oxaliplatin chemotherapy) to provide maximal systemic disease control and FDR-gemcitabine chemotherapy with concurrent IMRT (Radiation therapy) to address local disease, will achieve a significant improvement R0 resection (Radiation oncology repeat surgeries) rate in borderline resectable (surgical) pancreatic cancer and enhance disease free and overall survival in this patient population.
Read the detailed description
Gemcitabine has been the cornerstone of systemic therapy for pancreas cancer over this past decade. Recently, a combination of 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) was reported to have significant efficacy in advanced pancreatic cancer. Preclinical data suggests synergy between irinotecan and 5FU as well as between oxaliplatin and 5FU. Results of a phase II trial in advanced disease were reported in 2005 demonstrating a 26% confirmed response rate and median overall survival of 10.2 months. A follow-up phase III trial comparing FOLFIRINOX with gemcitabine for patients <75 years of age with advanced pancreatic cancer was presented at ASCO 2010 revealing improvement in PFS (6.4 vs 3.3 months, p=<.0001) and improved disease control rate (CR+PR+SD) (70.2% vs 50.9%, p=.0003). The most notable result was an impressive improvement in median overall survival with FOLFIRINOX compared to gemcitabine (11.1vs 6.8 months, p-value = <.0001, HR=.57). The main toxicity was grade 3/4 neutropenia (45.7% vs 18.7%, p=.0001) and increased risk of febrile neutropenia (5.4% vs 0.6%, p=.009)31.
- Conditions
- Pancreatic Cancer
- Being tested
- FOLFIRINOX, Intensity-modulated radiotherapy (IMRT), Surgical Exploration
- Keywords
- Neoadjuvant FOLFIRINOX, FDR-Gemcitabine, Concurrent, IMRT, Borderline Resectable 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.
FOLFIRINOXDrug
Starting dose levels as following:
Oxaliplatin 85mg/m2 intravenously over 120 minutes on day 1. Irinotecan 180mg/m2 intravenously over 90 minutes on day 1. NOTE: patients homozygous for the UGT1A1 (TA)7 promoter allele will be treated at an initial lower dose 140mg/m2 (please see Section 6.3.a) Leucovorin 400mg/m2 intravenously over 90 minutes on day 1. 5FU 400mg/m2 as bolus intravenous injection following leucovorin on day 1. 5FU 2,400mg/m2 infused intravenously as a continuous infusion over 46 hours following the bolus 5FU, beginning on day 1.
Intensity-modulated radiotherapy (IMRT)Radiation
50.0Gy in 2.0Gy per fraction
Surgical ExplorationProcedure or surgery
Patients without metastatic disease will be offered surgical exploration.
| Study group | Role | What they receive |
|---|---|---|
| Study Treatment | Experimental | Patients will receive FOLFIRINOX x 6 followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine (1g/m^2) on days 1, 8, 22, 29.
Intensity-modulated radiotherapy (IMRT): The prescribed dose was 50.0Gy in 2.0Gy per fraction.
Patients without metastatic disease will be offered surgical exploration. Receives: Drug: FOLFIRINOX; Radiation: Intensity-modulated radiotherapy (IMRT); Procedure: Surgical Exploration |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Percentage of Patients That Underwent an R0 Resection
To determine the frequency of achieving an R0 resection using a neoadjuvant regimen of FOLFIRINOX followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine in patients with borderline resectable pancreatic cancer. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.
Measured: 6 months
Secondary outcomes (2)
Median Progression-free Survival Time
To estimate progression-free survival as a function of time from study enrollment. Progression is defined as at least a 20% increase in the LD (longest diameter) of the primary lesion or the appearance of one or more new lesions
Measured: up to 2 years
Median Overall Survival Time
To estimate overall survival as a function of time from study enrollment.
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2012 (estimated)
- Study startJun 2011
- Primary completion10 Aug 2017
- Study completion30 Aug 2019
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 University of Michigan Rogel Cancer CenterThe 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
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Zalupski, MD, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01661088
- Sponsor's protocol ID
- UMCC 2011.007
- Other IDs
- HUM 47389
- Status last verified
- Oct 2019
- First submitted
- 24 Jul 2012
- Last updated
- 13 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Tran NH, Sahai V, Griffith KA, Nathan H, Kaza R, Cuneo KC, Shi J, Kim E, Sonnenday CJ, Cho CS, Lawrence TS, Zalupski MM. Phase 2 Trial of Neoadjuvant FOLFIRINOX and Intensity Modulated Radiation Therapy Concurrent With Fixed-Dose Rate-Gemcitabine in Patients With Borderline Resectable Pancreatic Cancer. Int J Radiat Oncol Biol Phys. 2020 Jan 1;106(1):124-133. doi: 10.1016/j.ijrobp.2019.08.057. Epub 2019 Sep 5.
PubMed 31494181
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Neoadjuvant FOLFIRINOX and FDR-Gemcitabine With Concurrent IMRT in Patients With Borderline Resectable Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT01661088
- Acronym / sponsor ID
- UMCC 2011.007
- Conditions
- Pancreatic Cancer
- Keywords
- Neoadjuvant FOLFIRINOX, FDR-Gemcitabine, Concurrent, IMRT, Borderline Resectable Pancreatic Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- 10 Aug 2017 (actual)
- Study completion
- 30 Aug 2019 (actual)
- First posted
- 9 Aug 2012 (estimated)
- Results
- Posted 8 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators hypothesize that the combination of the FOLFIRINOX regimen (a combination of 5-fluorouracil, irinotecan and oxaliplatin chemotherapy) to provide maximal systemic disease control and FDR-gemcitabine chemotherapy with concurrent IMRT (Radiation therapy) to address local disease, will achieve a significant improvement R0 resection (Radiation oncology repeat surgeries) rate in borderline resectable (surgical) pancreatic cancer and enhance disease free and overall survival in this patient population.
Detailed description
Gemcitabine has been the cornerstone of systemic therapy for pancreas cancer over this past decade. Recently, a combination of 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) was reported to have significant efficacy in advanced pancreatic cancer. Preclinical data suggests synergy between irinotecan and 5FU as well as between oxaliplatin and 5FU. Results of a phase II trial in advanced disease were reported in 2005 demonstrating a 26% confirmed response rate and median overall survival of 10.2 months. A follow-up phase III trial comparing FOLFIRINOX with gemcitabine for patients <75 years of age with advanced pancreatic cancer was presented at ASCO 2010 revealing improvement in PFS (6.4 vs 3.3 months, p=<.0001) and improved disease control rate (CR+PR+SD) (70.2% vs 50.9%, p=.0003). The most notable result was an impressive improvement in median overall survival with FOLFIRINOX compared to gemcitabine (11.1vs 6.8 months, p-value = <.0001, HR=.57). The main toxicity was grade 3/4 neutropenia (45.7% vs 18.7%, p=.0001) and increased risk of febrile neutropenia (5.4% vs 0.6%, p=.009)31.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Treatment | Experimental | Drug: FOLFIRINOX, Radiation: Intensity-modulated radiotherapy (IMRT), Procedure: Surgical ExplorationPatients will receive FOLFIRINOX x 6 followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine (1g/m^2) on days 1, 8, 22, 29. Intensity-modulated radiotherapy (IMRT): The prescribed dose was 50.0Gy in 2.0Gy per fraction. Patients without metastatic disease will be offered surgical exploration. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must have cytologic or histologic confirmation of carcinoma arising in the pancreas.
- Patients must be deemed to have borderline resectable disease with no radiologic evidence of distant metastatic disease prior to registration.
- Specifically, patients must have at least one designation of borderline resectable and no designation of unresectable disease.
- Patients must have a life expectancy of at least 12 weeks, a Zubrod performance status of < 1 and be willing and medically able to undergo surgical resection.
- Patients must have adequate organ function defined as follows: absolute neutrophil count of > 1500/mm3, platelets > 100,000/mm3, serum Cr < 1.5 mg/dl, total bilirubin < 2.0 mg/dl with relief of biliary obstruction if present (PTC tube or endobiliary stent).
Key exclusion criteria (6 listed)
- Patients with neuroendocrine tumors are excluded.
- Active systemic malignancy, ongoing infection, or any other serious uncontrolled, concomitant systemic disorders or psychiatric condition that would interfere with the safe delivery of protocol therapy.
- Patients with preexisting peripheral neuropathy > grade 2 are ineligible
- Pregnant or nursing women are ineligible.
- Patients must have no history of previous chemotherapy for pancreatic cancer or any abdominal radiation therapy.
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 |
|---|---|---|
| FOLFIRINOXStarting dose levels as following: Oxaliplatin 85mg/m2 intravenously over 120 minutes on day 1. Irinotecan 180mg/m2 intravenously over 90 minutes on day 1. NOTE: patients homozygous for the UGT1A1 (TA)7 promoter allele will be treated at an initial lower dose 140mg/m2 (please see Section 6.3.a) Leucovorin 400mg/m2 intravenously over 90 minutes on day 1. 5FU 400mg/m2 as bolus intravenous injection following leucovorin on day 1. 5FU 2,400mg/m2 infused intravenously as a continuous infusion over 46 hours following the bolus 5FU, beginning on day 1. | Drug | Study Treatment |
| Intensity-modulated radiotherapy (IMRT)50.0Gy in 2.0Gy per fraction | Radiation | Study Treatment |
| Surgical ExplorationPatients without metastatic disease will be offered surgical exploration. | Procedure or surgery | Study Treatment |
Primary outcome
The Percentage of Patients That Underwent an R0 Resection
Time frame: 6 months
To determine the frequency of achieving an R0 resection using a neoadjuvant regimen of FOLFIRINOX followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine in patients with borderline resectable pancreatic cancer. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.
2 secondary outcomes
Median Progression-free Survival Time
Time frame: up to 2 years
Median Overall Survival Time
Time frame: up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31494181Tran NH, Sahai V, Griffith KA, Nathan H, Kaza R, Cuneo KC, Shi J, Kim E, Sonnenday CJ, Cho CS, Lawrence TS, Zalupski MM. Phase 2 Trial of Neoadjuvant FOLFIRINOX and Intensity Modulated Radiation Therapy Concurrent With Fixed-Dose Rate-Gemcitabine in Patients With Borderline Resectable Pancreatic Cancer. Int J Radiat Oncol Biol Phys. 2020 Jan 1;106(1):124-133. doi: 10.1016/j.ijrobp.2019.08.057. Epub 2019 Sep 5.
Related trials for Pancreatic Cancer
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingPhase 1
Modified FOLFIRINOX and Pentamidine in Advanced and Metastatic Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma (PDAC)
RecruitingPhase 3
Atebimetinib + GnP as a First Line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma
Pancreatic Cancer, Pancreatic Cancer Metastatic
RecruitingPhase 3
Lanreotide Versus Placebo Before Surgery to Prevent a Surgical Complication Called a Pancreatic Fistula
Pancreatic Carcinoma, Pancreatic Neoplasm
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.
Mark Zalupski, MD principal investigator
University of Michigan Rogel Cancer Center
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 FOLFIRINOX, Intensity-modulated radiotherapy (IMRT) and Surgical Exploration in people with Pancreatic Cancer, run by University of Michigan Rogel Cancer Center 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 8 inclusion and 6 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 13 Nov 2019. 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 8 Aug 2018). 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?
The Percentage of Patients That Underwent an R0 Resection (time frame: 6 months). 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 NCT01661088, 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 13 Nov 2019.