Combination Chemotherapy Before and After Surgery in Treating Patients With Localized Pancreatic Cancer

Sponsor

Yale University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02047474

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

152.2

Anticipated Duration (Months)

5.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II trial studies how well combination chemotherapy before and after surgery works in treating patients with localized pancreatic cancer. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

Condition or Disease	Intervention/Treatment	Phase
Acinar Cell Adenocarcinoma of the Pancreas Duct Cell Adenocarcinoma of the Pancreas Stage I Pancreatic Cancer Stage IIA Pancreatic Cancer Stage IIB Pancreatic Cancer	Drug: oxaliplatin Drug: leucovorin calcium Drug: irinotecan hydrochloride Drug: fluorouracil Procedure: therapeutic conventional surgery Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

To determine the progression-free survival in patients with resectable non-metastatic pancreatic cancer treated with peri-operative modified leucovorin calcium, fluorouracil, irinotecan hydrochloride, oxaliplatin (mFOLFIRINOX).

SECONDARY OBJECTIVES:

Determine overall survival. II. Determine objective response rate after neoadjuvant mFOLFIRINOX.

TERTIARY OBJECTIVES:

Compare R0 resection rate and pathologic stage with institutional historical controls who did not receive neoadjuvant therapy.
Correlate early metabolic response, determined by changes in glucose metabolism using positron emission tomography (PET) scanning, with pathologic response, R0 resection, and pathologic stage.
Correlate early metabolic response, determined by changes in glucose metabolism using PET scanning, with progression-free and overall survival.
Correlate pre-operative response of CA19-9 with progression-free and overall survival.
Collect and bank serial serum and plasma specimens from subjects for future correlative biomarker studies.
Collect and bank tumor tissue from subjects prior to treatment (from the diagnostic endoscopic ultrasonography [EUS]-guided biopsy) and after treatment with six cycles of FOLFIRINOX (from the surgical specimen) for future correlative biomarker studies.

OUTLINE:

NEOADJUVANT THERAPY: Patients receive mFOLFIRINOX comprising oxaliplatin intravenously (IV) over 2 hours, levoleucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously for 46 hours on day 1. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

SURGERY: Beginning 3-8 weeks after completion of neoadjuvant therapy patients undergo surgical resection.

ADJUVANT THERARPY: Beginning within 12 weeks after surgery, patients receive mFOLFIRINOX as in neoadjuvant therapy. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 3 years, every 6 months for 2 years, and then annually thereafter.

Study Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Study of Peri-Operative Modified Folfirinox in Localized Pancreatic Cancer

Actual Study Start Date :

Mar 25, 2014

Anticipated Primary Completion Date :

Feb 1, 2026

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (mFOLFIRINOX) NEOADJUVANT THERAPY: Patients receive mFOLFIRINOX comprising oxaliplatin IV over 2 hours, levoleucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously for 46 hours on day 1. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Beginning 3-8 weeks after completion of neoadjuvant therapy patients undergo surgical resection. ADJUVANT THERARPY: Beginning within 12 weeks after surgery, patients receive mFOLFIRINOX as in neoadjuvant therapy. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: oxaliplatin Given IV Other Names: 1-OHP Dacotin Dacplat Eloxatin L-OHP Drug: leucovorin calcium Given IV Other Names: CF CFR LV Drug: irinotecan hydrochloride Given IV Other Names: Campto Camptosar CPT-11 irinotecan U-101440E Drug: fluorouracil Given IV Other Names: 5-fluorouracil 5-Fluracil 5-FU Procedure: therapeutic conventional surgery Undergo surgical resection Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (mFOLFIRINOX)

NEOADJUVANT THERAPY: Patients receive mFOLFIRINOX comprising oxaliplatin IV over 2 hours, levoleucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously for 46 hours on day 1. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Beginning 3-8 weeks after completion of neoadjuvant therapy patients undergo surgical resection. ADJUVANT THERARPY: Beginning within 12 weeks after surgery, patients receive mFOLFIRINOX as in neoadjuvant therapy. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: oxaliplatin

Given IV

Other Names:

1-OHP

Dacotin

Dacplat

Eloxatin

L-OHP

Drug: leucovorin calcium

Given IV

Other Names:

CFR

Drug: irinotecan hydrochloride

Given IV

Other Names:

Campto

Camptosar

CPT-11

irinotecan

U-101440E

Drug: fluorouracil

Given IV

Other Names:

5-fluorouracil

5-Fluracil

5-FU

Procedure: therapeutic conventional surgery

Undergo surgical resection

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Progression free survival rate [At 12 months]
Evaluated using a one-sided 0.10-alpha level exact test. Summarized using Kaplan-Meier curves

Secondary Outcome Measures

Overall survival [Up to 5 years]
Summarized using Kaplan-Meier curves.
Objective response rate [Up to 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Pathologic or cytologic documentation of pancreatic adenocarcinoma
Resectable pancreatic adenocarcinoma disease as defined as follows:
No evidence of extrapancreatic disease by cross sectional imaging, PET scan, or laparoscopy, including nodal involvement beyond the peripancreatic tissues and/or distant metastases;
No evidence of tumor extension to superior mesenteric artery, hepatic artery, celiac axis, aorta, or inferior vena cava, and no evidence of occlusion or encasement of the superior mesenteric vein or superior mesenteric vein/portal vein confluence, as assessed by computed tomography (CT) using pancreatic protocol (or magnetic resonance imaging [MRI] in patients who cannot undergo CT) and EUS
No prior treatment (chemotherapy, biological therapy, or radiotherapy) for resectable pancreatic cancer
No prior treatment with oxaliplatin, irinotecan (irinotecan hydrochloride), fluorouracil or capecitabine
Patients who received chemotherapy > 5 years ago for malignancies other than pancreatic cancer are eligible
There is no evidence of the second malignancy at the time of study entry
4 weeks since major surgery
No other concurrent anticancer therapy
Eastern Cooperative Oncology Group (ECOG) performance status: 0-1
No other malignancy within past five years except basal cell carcinoma of the skin, cervical carcinoma in situ, or non-metastatic prostate cancer
Paraffin block or slides must be available
Adequate organ function
No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
No >= grade 2 sensory peripheral neuropathy
No uncontrolled seizure disorder, active neurological disease, or known central nervous system (CNS) disease
No 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
No history of chronic diarrhea
Not pregnant and not nursing
No other medical condition or reason that, in the opinion of the investigator, would preclude study participation
Absolute neutrophil count >= 1,500/uL
Platelet count >= 100,000/uL
Hemoglobin >= 9 g/dL
Creatinine < 1.5 X upper limit of normal (ULN) or
Estimated glomerular filtration rate (GFR) > 30 ml/min
Bilirubin =< 1.5 X ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 X ULN
Negative pregnancy test in women of childbearing age

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Smilow Cancer Hospital at Fairfield	Fairfield	Connecticut	United States	06824
2	Smilow Cancer Hospital at Guilford	Guilford	Connecticut	United States	06437
3	Smilow Cancer Hospital at St. Francis Hospital	Hartford	Connecticut	United States	06105
4	Yale University	New Haven	Connecticut	United States	06520-8032
5	Smilow Cancer Hospital at North Haven	North Haven	Connecticut	United States	06473
6	Smilow Cancer Hospital at Orange	Orange	Connecticut	United States	06477
7	Smilow Cancer Hospital at Torrington	Torrington	Connecticut	United States	06790
8	Smilow Cancer Hospital at Trumbull	Trumbull	Connecticut	United States	06611
9	Smilow Cancer Hospital at Waterbury	Waterbury	Connecticut	United States	06708