Chemotherapy and Radiation Therapy Before Surgery Followed by Gemcitabine in Treating Patients with Pancreatic Cancer

NCT01821612 | Completed Early Phase 1

• 2 other identifiers: A021101U10CA031946
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 14

Brief Summary

This pilot clinical trial studies combination chemotherapy and radiation therapy before surgery followed by gemcitabine hydrochloride in treating patients with pancreatic cancer. Drugs used in chemotherapy, such as oxaliplatin, irinotecan hydrochloride, leucovorin calcium, fluorouracil, and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery.

Conditions

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Pancreatic Cancer

Outcome Measures

Primary Outcomes (4)

• Accrual rate, calculated by total number of patients accrued divided by number of months from the date the study is opened at the fifth site to the evaluation date

  Up to 3 years

• Rate of treatment-related toxicity during preoperative therapy assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4

  Up to 30 days after completion of study treatment

• Rate of treatment delay (greater than 4 weeks) during preoperative therapy

  Up to 28 weeks

• Completion rate of all preoperative and operative therapy

  Up to 30 weeks

Secondary Outcomes (6)

• Macroscopic (R0/R1) resection rate defined as number of patients achieved R0 or R1 resection during surgery divided by number of evaluable patients

  At the time of surgery

• Radiographic response rate defined as number of patients who achieved complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 during pre-operative therapy divided by the number of evaluable patients

  Up to 18 weeks

• Histopathologic response rate defined as number of patients who achieved CR or PR determined according to histopathologic examination during pre-operative therapy divided by the number of evaluable patients

  Up to 18 weeks

• Time to locoregional recurrence

  From the date of registration to the date of the first documented locoregional recurrence, assessed up to 3 years

• Time to distant recurrence

  From the date of registration to the date of the first documented distant recurrence, assessed up to 3 years

Study Arms (1)

mFOLFIRINOX, chemoradiation, surgery and gemcitabine

OTHER

Each patient will receive mFOLFIRINOX therapy administered every other week for a total of 4 cycles. Each treatment cycle is a total of 14 days. This treatment program consists of four drugs (oxaliplatin 85 mg/m\^2 IV over 2 hours on day 1 followed by irinotecan 180 mg/m\^2 IV over 90 minutes on day 1 followed by, leucovorin 400 mg/m\^2 IV over 2 hours on day 1 followed by 5-FU 2400 mg/m\^2 IV over 46-48 hours). Two to six weeks following treatment with the mFOLFIRINOX, if the tumor has not spread to other parts of the body then the patient will receive capecitabine 825 mg/m\^2, twice daily for 28 days along with radiation therapy. Patients will have surgery within 4-10 weeks of the last dose of chemoradiation if the tumor has gotten smaller or stayed the same. Within 6-8 weeks following surgery, patients will receive gemcitabine for 2 cycles (1 cycle is 28 days). Gemcitabine will be given IV on days 1, 8 and 15 of every 28 day cycle.

Drug: oxaliplatin; Drug: irinotecan; Drug: leucovorin; Drug: 5-fluorouracil; Drug: capecitabine; Radiation: radiation; Procedure: surgery; Drug: gemcitabine

Interventions

oxaliplatin DRUG

IV

mFOLFIRINOX, chemoradiation, surgery and gemcitabine

irinotecan DRUG

IV

mFOLFIRINOX, chemoradiation, surgery and gemcitabine

leucovorin DRUG

IV

mFOLFIRINOX, chemoradiation, surgery and gemcitabine

5-fluorouracil DRUG

IV

mFOLFIRINOX, chemoradiation, surgery and gemcitabine

capecitabine DRUG

PO

mFOLFIRINOX, chemoradiation, surgery and gemcitabine

radiation RADIATION

mFOLFIRINOX, chemoradiation, surgery and gemcitabine

surgery PROCEDURE

mFOLFIRINOX, chemoradiation, surgery and gemcitabine

gemcitabine DRUG

IV

mFOLFIRINOX, chemoradiation, surgery and gemcitabine

Eligibility Criteria

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

Pre-Registration Eligibility Criteria * Documentation of Disease and Radiographic Staging * Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinate process * Objective radiographic staging with a) contrast-enhanced, helical thin-cut computed tomography (CT)/magnetic resonance imaging (MRI) scan of the abdomen and b) CT scan/MRI of the chest * Note: echoendoscopic staging will be permitted as an adjunctive modality, but all stage definitions below will be determined using CT/MRI as outlined below. In the event echoendoscopic stage and CT/MRI stage are discordant, the CT/MRI stage will be used. Significant discordance should be discussed with the study principal investigator (PI) prior to enrollment * Borderline resectable primary tumor, defined by the presence of any one or more of the following on CT/MRI, and confirmed by central radiographic review: * An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring ≥ 180 degrees of the circumference of the vessel wall * Short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction * Short segment interface (of any degree) between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction * An interface between the tumor and superior mesenteric artery (SMA) measuring \< 180 degrees of the circumference of the vessel wall * No potentially resectable disease defined as primary tumors with all of the following: * An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring \< 180 degrees of the circumference of the vessel wall * No radiographic interface between the tumor and the (superior mesenteric artery) SMA, hepatic artery or celiac axis * No radiographic evidence of metastatic disease * No metastatic disease defined as any one or more of the following: * Suspicious lymphadenopathy outside the standard surgical field (i.e., aortocaval nodes, distant abdominal nodes) * Radiographic evidence for metastatic disease in distant organs, such as masses in distant organs or ascites * No locally advanced and/or unresectable disease clearly defined by any one or more of the following by CT/MRI: * An interface between the tumor and the SMA measuring ≥ 180 degrees of the circumference of the vessel wall * No interface between the tumor and the aorta * Occlusion of the SMV or portal vein without a sufficient cuff of normal vein above and below the level of obstruction with which to perform venous reconstruction * Long-segment interface (of any degree) between the tumor and the common hepatic artery or its major tributaries with insufficient artery proximal and distal to the interface to perform reconstruction * No prior chemotherapy or chemoradiation for pancreatic cancer * No patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years * Baseline peripheral sensory neuropathy must be grade \< 2 * No patients with known Gilbert's Syndrome or homozygosity for UGT1A1\*28 polymorphism * No history of pulmonary embolism in the past 6 months * Age ≥ 18 years of age * Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status 0-1 * Pregnancy/Nursing Status: Non-pregnant and non-breast-feeding. Female participants of child-bearing potential must have a negative urine or serum pregnancy test prior to registration. Perimenopausal participants must be amenorrheic \> 12 months to be considered not of childbearing potential. * Required Pre-Registration Laboratory Values: * Granulocytes ≥ 2,000/ul * Hemoglobin \> 9 g/dL * Platelets ≥ 100,000/ul * Albumin \> 3.0 g/dL * Creatinine ≤1.5 x upper limit of normal (ULN) Registration Eligibility Criteria * Confirmation of pre-registration eligibility criteria as described under "Documentation of Disease and Radiographic Staging" by the Alliance Central Radiographic Review * Required Registration Laboratory Values: * Bilirubin ≤2 mg/dl * AST (SGOT) \& ALT (SGPT) ≤ 2.5 x ULN

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (14)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

The James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, 40202, United States

Location

Ochsner Medical Center Jefferson

New Orleans, Louisiana, 70121, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University Pointe

West Chester, Ohio, 45069, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Katz MH, Shi Q, Ahmad SA, Herman JM, Marsh Rde W, Collisson E, Schwartz L, Frankel W, Martin R, Conway W, Truty M, Kindler H, Lowy AM, Bekaii-Saab T, Philip P, Talamonti M, Cardin D, LoConte N, Shen P, Hoffman JP, Venook AP. Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer: Alliance for Clinical Trials in Oncology Trial A021101. JAMA Surg. 2016 Aug 17;151(8):e161137. doi: 10.1001/jamasurg.2016.1137. Epub 2016 Aug 17.

  PMID: 27275632 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Oxaliplatin; Irinotecan; Leucovorin; Fluorouracil; Capecitabine; Radiation; Surgical Procedures, Operative; Gemcitabine

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; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Physical Phenomena

Study Officials

• Matthew Katz, M.D.

  M.D. Anderson Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2013
• First Posted: April 1, 2013
• Study Start: May 29, 2013
• Primary Completion: November 1, 2014
• Study Completion: June 15, 2018
• Last Updated: January 13, 2025

Record last verified: 2025-01

Locations

US (14)