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

NCT03099265 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 2000020432
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 40 weeks

Secondary Outcomes (6)

• Number of Participants Response to Neoadjuvant Therapy Using RECIST

  Up to 40 weeks

• Number of Participants With and Without Pathologic Response to Neoadjuvant Therapy

  Up to 40 weeks

• Number of Participants With and Without Recurrence

  Up to 40 weeks

• Number of Participants: Progression Free Survival

  Up to 2 years

• Number of Participants: Overall Survival

  Up to 2 years

Study Arms (1)

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.

Drug: neoadjuvant mFOLFIRINOX; Drug: Stereotactic body radiotherapy (SBRT)

Interventions

neoadjuvant mFOLFIRINOX DRUG

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.

Also known as: Oxaliplatin, Irinotecan, Leucovorin, 5-fluorouracil, folinic acid

patients with borderline resectable pancreatic adenocarcinoma

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.

patients with borderline resectable pancreatic adenocarcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Smilow Cancer Hospital

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Oxaliplatin; Irinotecan; Leucovorin; Fluorouracil; Radiosurgery

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Kimberly L. Johung, MD, PhD Associate Professor of Therapeutic Radiology
• Organization: Yale School of Medicine

kimberly.johung@yale.edu

(203) 200-2008

Study Officials

• Kimberly Johung, MD, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2017
• First Posted: April 4, 2017
• Study Start: June 26, 2017
• Primary Completion: September 18, 2019
• Study Completion: September 18, 2019
• Last Updated: October 27, 2022
• Results First Posted: October 27, 2022

Record last verified: 2022-09

Locations

US (1)