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Neoadjuvant Modified FOLFIRINOX and Stereotactic Body Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma

Primary Purpose

Pancreatic Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

neoadjuvant mFOLFIRINOX

Stereotactic body radiotherapy (SBRT)

About this trial

This is an interventional treatment trial for Pancreatic Cancer

Eligibility Criteria

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

Inclusion Criteria:

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
- 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

Exclusion Criteria:

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
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

Sites / Locations

Smilow Cancer Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

patients with borderline resectable pancreatic adenocarcinoma

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT03099265

First Posted

March 28, 2017

Last Updated

September 29, 2022

Sponsor

Yale University

1. Study Identification

Unique Protocol Identification Number

NCT03099265

Brief Title

Neoadjuvant Modified FOLFIRINOX and Stereotactic Body Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma

Official Title

Phase II Study to Evaluate Neoadjuvant Modified FOLFIRINOX and Stereotactic Body Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Terminated

Why 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.

Study Start Date

June 26, 2017 (Actual)

Primary Completion Date

September 18, 2019 (Actual)

Study Completion Date

September 18, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yale University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

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

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

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

patients with borderline resectable pancreatic adenocarcinoma

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

neoadjuvant mFOLFIRINOX

Other Intervention Name(s)

Oxaliplatin, Irinotecan, Leucovorin, 5-fluorouracil, folinic acid

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Stereotactic body radiotherapy (SBRT)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of Participants With and Without R0 Resection

Description

Time Frame

Up to 40 weeks

Secondary Outcome Measure Information:

Title

Number of Participants Response to Neoadjuvant Therapy Using RECIST

Description

Time Frame

Up to 40 weeks

Title

Number of Participants With and Without Pathologic Response to Neoadjuvant Therapy

Description

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.

Time Frame

Up to 40 weeks

Title

Number of Participants With and Without Recurrence

Description

Number of participants with and without recurrence following surgery. This outcome was updated when the results were entered.

Time Frame

Up to 40 weeks

Title

Number of Participants: Progression Free Survival

Description

Presented are count of patients that had experienced either progression free survival or disease progression through the follow up period.

Time Frame

Up to 2 years

Title

Number of Participants: Overall Survival

Description

Presented are counts of patients that we either deceased or not deceased at the end of the follow up period.

Time Frame

Up to 2 years

Title

Grade 3 or Greater Acute and Late Gastrointestinal Toxicity

Description

Time Frame

Up to 40 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 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 Exclusion Criteria: 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kimberly Johung, MD, PhD

Organizational Affiliation

Yale University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Smilow Cancer Hospital

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06510

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

Neoadjuvant Modified FOLFIRINOX and Stereotactic Body Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma

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