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

NCT ID: NCT02047474

Last Updated: 2023-11-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-25
• Study Completion Date: 2026-12-31

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.

Detailed Description

PRIMARY OBJECTIVES:

I. 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:

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

TERTIARY OBJECTIVES:

I. Compare R0 resection rate and pathologic stage with institutional historical controls who did not receive neoadjuvant therapy.

II. Correlate early metabolic response, determined by changes in glucose metabolism using positron emission tomography (PET) scanning, with pathologic response, R0 resection, and pathologic stage.

III. Correlate early metabolic response, determined by changes in glucose metabolism using PET scanning, with progression-free and overall survival.

IV. Correlate pre-operative response of CA19-9 with progression-free and overall survival.

V. Collect and bank serial serum and plasma specimens from subjects for future correlative biomarker studies.

VI. 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.

Conditions

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Stage I Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

oxaliplatin

Intervention Type: DRUG

Given IV

leucovorin calcium

Intervention Type: DRUG

Given IV

irinotecan hydrochloride

Intervention Type: DRUG

Given IV

fluorouracil

Intervention Type: DRUG

Given IV

therapeutic conventional surgery

Intervention Type: PROCEDURE

Undergo surgical resection

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

oxaliplatin

Given IV

Intervention Type: DRUG

leucovorin calcium

Given IV

Intervention Type: DRUG

irinotecan hydrochloride

Given IV

Intervention Type: DRUG

fluorouracil

Given IV

Intervention Type: DRUG

therapeutic conventional surgery

Undergo surgical resection

Intervention Type: PROCEDURE

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

1-OHP; Dacotin; Dacplat; Eloxatin; L-OHP; CF; CFR; LV; Campto; Camptosar; CPT-11; irinotecan; U-101440E; 5-fluorouracil; 5-Fluracil; 5-FU

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jill Lacy, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Smilow Cancer Hospital at Fairfield

Fairfield, Connecticut, United States

Smilow Cancer Hospital at Guilford

Guilford, Connecticut, United States

Smilow Cancer Hospital at St. Francis Hospital

Hartford, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Smilow Cancer Hospital at North Haven

North Haven, Connecticut, United States

Smilow Cancer Hospital at Orange

Orange, Connecticut, United States

Smilow Cancer Hospital at Torrington

Torrington, Connecticut, United States

Smilow Cancer Hospital at Trumbull

Trumbull, Connecticut, United States

Smilow Cancer Hospital at Waterbury

Waterbury, Connecticut, United States

Countries

United States

References

Cecchini M, Salem RR, Robert M, Czerniak S, Blaha O, Zelterman D, Rajaei M, Townsend JP, Cai G, Chowdhury S, Yugawa D, Tseng R, Mejia Arbelaez C, Jiao J, Shroyer K, Thumar J, Kortmansky J, Zaheer W, Fischbach N, Persico J, Stein S, Khan SA, Cha C, Billingsley KG, Kunstman JW, Johung KL, Wiess C, Muzumdar MD, Spickard E, Aushev VN, Laliotis G, Jurdi A, Liu MC, Escobar-Hoyos L, Lacy J. Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer: A Nonrandomized Controlled Trial. JAMA Oncol. 2024 Aug 1;10(8):1027-1035. doi: 10.1001/jamaoncol.2024.1575.

Reference Type: DERIVED

PMID: 38900452 (View on PubMed)

Other Identifiers

NCI-2013-02349

Identifier Type: REGISTRY

Identifier Source: secondary_id

1306012255

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA016359

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1306012255

Identifier Type: -

Identifier Source: org_study_id