- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01643499
Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies
A Genotype-guided Dosing Study of mFOLFIRINOX in Previously Untreated Patients With Advanced Gastrointestinal Malignancies
Study Overview
Status
Conditions
- Mucinous Adenocarcinoma of the Rectum
- Signet Ring Adenocarcinoma of the Rectum
- Stage IIIA Rectal Cancer
- Stage IIIB Rectal Cancer
- Stage IIIC Rectal Cancer
- Acinar Cell Adenocarcinoma of the Pancreas
- Duct Cell Adenocarcinoma of the Pancreas
- Stage III Pancreatic Cancer
- Stage IV Pancreatic Cancer
- Mucinous Adenocarcinoma of the Colon
- Signet Ring Adenocarcinoma of the Colon
- Stage IIIA Colon Cancer
- Stage IIIB Colon Cancer
- Stage IIIC Colon Cancer
- Stage IV Gastric Cancer
- Advanced Adult Primary Liver Cancer
- Localized Unresectable Adult Primary Liver Cancer
- Unresectable Extrahepatic Bile Duct Cancer
- Stage IVA Colon Cancer
- Stage IVA Rectal Cancer
- Stage IVB Colon Cancer
- Stage IVB Rectal Cancer
- Stage IIIA Gallbladder Cancer
- Stage IIIB Gallbladder Cancer
- Stage IVA Gallbladder Cancer
- Stage IVB Gallbladder Cancer
- Diffuse Adenocarcinoma of the Stomach
- Intestinal Adenocarcinoma of the Stomach
- Mixed Adenocarcinoma of the Stomach
- Stage IIIA Gastric Cancer
- Stage IIIB Gastric Cancer
- Stage IIIC Gastric Cancer
- Cholangiocarcinoma of the Extrahepatic Bile Duct
- Cholangiocarcinoma of the Gallbladder
- Adenocarcinoma of the Gallbladder
- Adult Primary Cholangiocellular Carcinoma
- Metastatic Extrahepatic Bile Duct Cancer
- Adenocarcinoma of Unknown Primary
- Metastatic Carcinoma of Unknown Primary
- Newly Diagnosed Carcinoma of Unknown Primary
Detailed Description
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
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Illinois
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Chicago, Illinois, United States, 60637-1470
- University of Chicago Comprehensive Cancer Center
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Evanston, Illinois, United States, 60201
- Evanston CCOP-NorthShore University HealthSystem
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / 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.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
4 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Response rates (by RECIST 1.1) for patients with each different type of gastrointestinal malignancy
Time Frame: Up to 1 year
|
Up to 1 year
|
Cumulative dose intensity of irinotecan hydrochloride
Time Frame: Up to 1 year
|
Up to 1 year
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Stomach Diseases
- Endocrine Gland Neoplasms
- Liver Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Neoplastic Processes
- Colorectal Neoplasms
- Gallbladder Diseases
- Biliary Tract Diseases
- Pancreatic Diseases
- Neoplasm Metastasis
- Neoplasms, Cystic, Mucinous, and Serous
- Bile Duct Diseases
- Biliary Tract Neoplasms
- Stomach Neoplasms
- Carcinoma
- Adenocarcinoma
- Rectal Neoplasms
- Pancreatic Neoplasms
- Cholangiocarcinoma
- Liver Neoplasms
- Cystadenocarcinoma
- Colonic Neoplasms
- Adenocarcinoma, Mucinous
- Neoplasms, Unknown Primary
- Carcinoma, Acinar Cell
- Gallbladder Neoplasms
- Bile Duct Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Topoisomerase Inhibitors
- Micronutrients
- Vitamins
- Calcium-Regulating Hormones and Agents
- Topoisomerase I Inhibitors
- Antidotes
- Vitamin B Complex
- Fluorouracil
- Oxaliplatin
- Leucovorin
- Irinotecan
- Calcium
- Levoleucovorin
Other Study ID Numbers
- 12-0033
- NCI-2012-00585 (REGISTRY: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Case Comprehensive Cancer CenterNational Cancer Institute (NCI)WithdrawnMucinous Adenocarcinoma of the Rectum | Signet Ring Adenocarcinoma of the Rectum | Mucinous Adenocarcinoma of the Colon | Signet Ring Adenocarcinoma of the Colon | Stage I Colon Cancer | Stage I Rectal Cancer
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John HaysSanofiUnknownMucinous Adenocarcinoma of the Rectum | Signet Ring Adenocarcinoma of the Rectum | Mucinous Adenocarcinoma of the Colon | Signet Ring Adenocarcinoma of the Colon | Stage IV Colon Cancer | Stage IV Rectal CancerUnited States
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National Cancer Institute (NCI)TerminatedMucinous Adenocarcinoma of the Rectum | Signet Ring Adenocarcinoma of the Rectum | Mucinous Adenocarcinoma of the Colon | Signet Ring Adenocarcinoma of the Colon | Stage IV Colon Cancer | Stage IV Rectal Cancer | Recurrent Colon Cancer | Recurrent Rectal Cancer | Adenocarcinoma of the Rectum | Adenocarcinoma...United States
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John HaysAmgenUnknownMucinous Adenocarcinoma of the Rectum | Signet Ring Adenocarcinoma of the Rectum | Mucinous Adenocarcinoma of the Colon | Signet Ring Adenocarcinoma of the Colon | Stage IV Colon Cancer | Stage IV Rectal Cancer | Recurrent Colon Cancer | Recurrent Rectal CancerUnited States
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Fox Chase Cancer CenterNational Cancer Institute (NCI)TerminatedMucinous Adenocarcinoma of the Rectum | Signet Ring Adenocarcinoma of the Rectum | Stage IIIA Rectal Cancer | Stage IIIB Rectal Cancer | Stage IIIC Rectal Cancer | Mucinous Adenocarcinoma of the Colon | Signet Ring Adenocarcinoma of the Colon | Stage IIIA Colon Cancer | Stage IIIB Colon Cancer | Stage... and other conditionsUnited States
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