Clinical trial NCT03099265: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pancreatic Cancer
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2017-04-04
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With and Without R0 Resection
timeFrame: Up to 40 weeks
Secondary outcomes:
measure: Number of Participants Response to Neoadjuvant Therapy Using RECIST
timeFrame: Up to 40 weeks
measure: Number of Participants With and Without Pathologic Response to Neoadjuvant Therapy
timeFrame: Up to 40 weeks
measure: Number of Participants With and Without Recurrence
timeFrame: Up to 40 weeks
measure: Number of Participants: Progression Free Survival
timeFrame: Up to 2 years
measure: Number of Participants: Overall Survival
timeFrame: Up to 2 years
measure: Grade 3 or Greater Acute and Late Gastrointestinal Toxicity
timeFrame: Up to 40 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Smilow Cancer Hospital
state: Connecticut
Study officials:
affiliation: Yale University
name: Kimberly Johung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: