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A Study of Neoadjuvant FOLFIRINOX and FDR-Gemcitabine With Concurrent IMRT in Patients

Primary Purpose

Pancreatic Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

FOLFIRINOX

Intensity-modulated radiotherapy (IMRT)

Surgical Exploration

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring Neoadjuvant FOLFIRINOX, FDR-Gemcitabine, Concurrent, IMRT, Borderline Resectable Pancreatic Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

University of Michigan Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Study Treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Median Overall Survival Time

To estimate overall survival as a function of time from study enrollment.

Full Information

NCT ID

NCT01661088

First Posted

July 24, 2012

Last Updated

October 29, 2019

Sponsor

University of Michigan Rogel Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT01661088

Brief Title

A Study of Neoadjuvant FOLFIRINOX and FDR-Gemcitabine With Concurrent IMRT in Patients

Official Title

A Phase II Study of Neoadjuvant FOLFIRINOX and FDR-Gemcitabine With Concurrent IMRT in Patients With Borderline Resectable Pancreatic Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

June 2011 (undefined)

Primary Completion Date

August 10, 2017 (Actual)

Study Completion Date

August 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Michigan Rogel Cancer Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Cancer

Keywords

Neoadjuvant FOLFIRINOX, FDR-Gemcitabine, Concurrent, IMRT, Borderline Resectable Pancreatic Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Study Treatment

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

FOLFIRINOX

Intervention Description

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.

Intervention Type

Radiation

Intervention Name(s)

Intensity-modulated radiotherapy (IMRT)

Intervention Description

50.0Gy in 2.0Gy per fraction

Intervention Type

Procedure

Intervention Name(s)

Surgical Exploration

Intervention Description

Patients without metastatic disease will be offered surgical exploration.

Primary Outcome Measure Information:

Title

The Percentage of Patients That Underwent an R0 Resection

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Median Progression-free Survival Time

Description

Time Frame

up to 2 years

Title

Median Overall Survival Time

Description

To estimate overall survival as a function of time from study enrollment.

Time Frame

up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark Zalupski, MD

Organizational Affiliation

University of Michigan Rogel Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Michigan Comprehensive Cancer Center

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31494181

Citation

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.

Results Reference

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A Study of Neoadjuvant FOLFIRINOX and FDR-Gemcitabine With Concurrent IMRT in Patients

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