Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies

Summary

This study is being done to determine the dose of a chemotherapy drug (irinotecan \[irinotecan hydrochloride\]) that can be tolerated as part of a combination of drugs. There is a combination of chemotherapy drugs often used to treat gastrointestinal cancer, which consists of 5-FU (fluorouracil), leucovorin (leucovorin calcium), irinotecan and oxaliplatin and is known as "FOLFIRINOX". FOLFIRINOX is a current drug therapy combination (or regimen) used for people with advanced pancreatic cancer, although this combination is not Food and Drug Administration (FDA) approved for this indication. FOLFIRINOX was recently shown in a separate clinical trial to increase survival compared to another commonly used drug in pancreatic cancer called gemcitabine. FOLFIRINOX is also a reasonable regimen for those with other advanced cancers of the gastrointestinal tract, including colon cancer, rectal cancer, esophagus cancer, stomach cancer, gall bladder cancer, bile duct cancer, ampullary cancer, and cancers with an unknown primary location. The best dose of irinotecan to use in FOLFIRINOX is not known. This study will analyze one gene (uridine 5'-diphospho \[UDP\] glucuronosyltransferase 1 family, polypeptide A1 \[UGT1A1\] gene) of subjects for the presence of an alteration in that gene, which may affect how the body handles irinotecan. Genes help determine some of the investigators individual characteristics, such as eye color, height and skin tone. Genes may also determine why people get certain diseases and how medicines may affect them. The result of the genetic analysis will divide subjects into one of three groups: A, B, or C. Group A (approximately 45% of subjects) will receive the standard dose of irinotecan. Group B (approximately 45% of subjects) will receive a lower dose of irinotecan. Group C (approximately 10% of subjects) will receive an even lower dose of irinotecan

Conditions

• Acinar Cell Adenocarcinoma of the Pancreas
• Adenocarcinoma of the Gallbladder
• Adenocarcinoma of Unknown Primary
• Adult Primary Cholangiocellular Carcinoma
• Advanced Adult Primary Liver Cancer
• Cholangiocarcinoma of the Extrahepatic Bile Duct
• Cholangiocarcinoma of the Gallbladder
• Diffuse Adenocarcinoma of the Stomach
• Duct Cell Adenocarcinoma of the Pancreas
• Intestinal Adenocarcinoma of the Stomach
• Localized Unresectable Adult Primary Liver Cancer
• Metastatic Carcinoma of Unknown Primary
• Metastatic Extrahepatic Bile Duct Cancer
• Mixed Adenocarcinoma of the Stomach
• Mucinous Adenocarcinoma of the Colon
• Mucinous Adenocarcinoma of the Rectum
• Newly Diagnosed Carcinoma of Unknown Primary
• Signet Ring Adenocarcinoma of the Colon
• Signet Ring Adenocarcinoma of the Rectum
• Stage III Pancreatic Cancer
• Stage IIIA Colon Cancer
• Stage IIIA Gallbladder Cancer
• Stage IIIA Gastric Cancer
• Stage IIIA Rectal Cancer
• Stage IIIB Colon Cancer
• Stage IIIB Gallbladder Cancer
• Stage IIIB Gastric Cancer
• Stage IIIB Rectal Cancer
• Stage IIIC Colon Cancer
• Stage IIIC Gastric Cancer
• Stage IIIC Rectal Cancer
• Stage IV Gastric Cancer
• Stage IV Pancreatic Cancer
• Stage IVA Colon Cancer
• Stage IVA Gallbladder Cancer
• Stage IVA Rectal Cancer
• Stage IVB Colon Cancer
• Stage IVB Gallbladder Cancer
• Stage IVB Rectal Cancer
• Unresectable Extrahepatic Bile Duct Cancer

Interventions

DRUG

oxaliplatin

Given IV

DRUG

irinotecan hydrochloride

Given IV

DRUG

leucovorin calcium

Given IV

DRUG

fluorouracil

Given IV

OTHER

laboratory biomarker analysis

Correlative studies

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• University of Chicago

  lead OTHER

Principal Investigators

• Hedy Kindler · University of Chicago Comprehensive Cancer Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-03-26

Primary Completion

2016-08-28

Completion

2019-07-31

Countries

• United States

Study Locations