Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies
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ClinicalTrials.gov Identifier: NCT01643499 |
Recruitment Status
:
Active, not recruiting
First Posted
: July 18, 2012
Last Update Posted
: March 12, 2018
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Condition or disease | Intervention/treatment | Phase |
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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 | Drug: oxaliplatin Drug: irinotecan hydrochloride Drug: leucovorin calcium Drug: fluorouracil Other: laboratory biomarker analysis | Phase 1 |
PRIMARY OBJECTIVES:
I. To determine the dose-limiting toxicity (DLT) rate in cycle #1 in each of two UGT1A1 genotype groups (*1*1, *1*28) using genotype-guided dosing of irinotecan as part of the modified (m) FOLFIRINOX regimen.
SECONDARY OBJECTIVES:
I. To determine the cumulative dose intensity of irinotecan achieved in each genotype group.
II. To determine the response rates by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) for each different disease (pancreatic cancer, biliary cancers, gastric cancer, colorectal cancer, adenocarcinoma of unknown primary) treated in the study.
OUTLINE:
Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan hydrochloride IV over 1.5 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on days 1 and 15. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 79 participants |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Genotype-guided Dosing Study of mFOLFIRINOX in Previously Untreated Patients With Advanced Gastrointestinal Malignancies |
Actual Study Start Date : | March 26, 2012 |
Actual Primary Completion Date : | August 28, 2016 |
Estimated Study Completion Date : | August 2020 |

Arm | Intervention/treatment |
---|---|
Experimental: Treatment (mFOLFIRINOX)
Patients receive oxaliplatin IV over 2 hours on, irinotecan hydrochloride IV over 1.5 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on days 1 and 15. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
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Drug: oxaliplatin
Given IV
Other Names:
Drug: irinotecan hydrochloride
Given IV
Other Names:
Drug: leucovorin calcium
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
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- DLT rate in course 1 for each of the two most common genotype groups (*1*1 and *1*28) [ Time Frame: 4 weeks ]To show that the DLT rate is less than 33% with at least 70-80% confidence, which is comparable to the standard 3+3 phase I design with 0 out of 3 or 1 out of 6 patients experiencing a DLT.
- Response rates (by RECIST 1.1) for patients with each different type of gastrointestinal malignancy [ Time Frame: Up to 1 year ]
- Cumulative dose intensity of irinotecan hydrochloride [ Time Frame: Up to 1 year ]

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histologically or cytologically confirmed locally advanced or metastatic pancreatic adenocarcinoma, colorectal adenocarcinoma, gastric adenocarcinoma, cholangiocarcinoma, gall bladder adenocarcinoma, ampullary carcinoma, adenocarcinoma of unclear primary (with a gastrointestinal primary suspected), or other primary gastrointestinal malignancy for which the treating physician feels that mFOLFIRINOX is a reasonable therapeutic option.
- Amendment (January 2014): only subjects with the following histologies will be eligible
Cohort # 1 (pancreatic cohort): locally advanced or metastatic pancreatic adenocarcinoma (19 subjects evaluable for the primary endpoint after the amendment)
Cohort #2 (biliary tract cohort): locally advanced or metastatic cholangiocarcinoma, gall bladder adenocarcinoma, or ampullary carcinoma (19 subjects evaluable for the primary endpoint after the amendment). Patients with adenocarcinoma of unclear primary that are most likely of biliary tract origin (in the opinion of the treating physician) will also be allowed on this cohort.
- Patients with a history of obstructive jaundice due to the primary tumor must have a metal biliary stent in place,
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1,
- Life expectancy > 3 months,
- Absolute neutrophil count (ANC) >= l500/ul,
- Hemoglobin >= 9g/dL,
- Platelets >= 100,000/ ul,
- Total bilirubin < 1.5 x upper limit of normal,
- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) < 2.5 x upper limit of normal for patients without liver metastases OR SGOT and SGPT < 5 x upper limit of normal for patients with liver metastases,
- Creatinine =< 1.5 x upper limit of normal,
- Measurable or non-measurable disease will be allowed,
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, up until 30 days after final study treatment; should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately,
- Patients taking substrates, inhibitors, or inducers of Cytochrome P450 3A4 (CYP3A4) should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions with irinotecan
- Signed informed consent.
Exclusion Criteria:
- Prior chemotherapy or radiation therapy for any cancer,
- Inflammatory bowel disease (Crohn's disease, ulcerative colitis),
- Diarrhea, grade 1 or greater by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v. 4.0); pancreatic cancer patients with clinical evidence of pancreatic insufficiency must be taking pancreatic enzyme replacement,
- Neuropathy, grade 2 or greater by NCI-CTCAE, v. 4.0,
- Documented brain metastases,
- Serious underlying medical or psychiatric illnesses that would, in the opinion of the treating physician, substantially increase the risk for complications related to treatment,
- Active uncontrolled bleeding,
- Pregnancy or breastfeeding,
- Major surgery within 4 weeks,
- Previous or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer for which the patient has been previously treated and the lifetime recurrence risk is less than 30%,
- Patients with any polymorphism in UGT1A1 other than *1 or *28.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01643499
United States, Illinois | |
University of Chicago Comprehensive Cancer Center | |
Chicago, Illinois, United States, 60637-1470 | |
Evanston CCOP-NorthShore University HealthSystem | |
Evanston, Illinois, United States, 60201 |
Principal Investigator: | Hedy Kindler | University of Chicago Comprehensive Cancer Center |
Responsible Party: | University of Chicago |
ClinicalTrials.gov Identifier: | NCT01643499 History of Changes |
Other Study ID Numbers: |
12-0033 NCI-2012-00585 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) |
First Posted: | July 18, 2012 Key Record Dates |
Last Update Posted: | March 12, 2018 |
Last Verified: | March 2018 |
Additional relevant MeSH terms:
Carcinoma Adenocarcinoma Pancreatic Neoplasms Stomach Neoplasms Rectal Neoplasms Colonic Neoplasms Liver Neoplasms Cholangiocarcinoma Gallbladder Neoplasms Bile Duct Neoplasms Neoplasms, Unknown Primary Adenocarcinoma, Mucinous Cystadenocarcinoma Carcinoma, Acinar Cell Neoplasms, Glandular and Epithelial |
Neoplasms by Histologic Type Neoplasms Digestive System Neoplasms Neoplasms by Site Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Gastrointestinal Neoplasms Gastrointestinal Diseases Stomach Diseases Colorectal Neoplasms Intestinal Neoplasms Intestinal Diseases Rectal Diseases |