Anal CancerPhase 1NCT00654160
Irinotecan, Fluorouracil, and Leucovorin in Treating Patients With Advanced Gastrointestinal Cancer
A Phase 1 study testing fluorouracil, irinotecan hydrochloride and leucovorin calcium in people with Anal Cancer and Carcinoma of the Appendix, run by Mayo Clinic at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as irinotecan, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Anal Cancer, Carcinoma of the Appendix, Colorectal Cancer
- What is being tested?
- fluorouracil, irinotecan hydrochloride and leucovorin calcium
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to 3 Dec 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Life expectancy ≥ 12 weeks.
- ECOG performance status 0-2
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- SGOT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN if liver metastases)
- Total Bilirubin ≤ ULN for patients in group 3 and ≤ 2.0 times ULN for patients in groups 1 and 2
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- Hemoglobin ≥ 9.0 g/dL
- Creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception for the duration of study treatment
- Willing to provide blood samples for mandatory translational studies
Who cannot join
- Known allergy to irinotecan hydrochloride-related agents (e.g., topotecan), 5-fluorouracil, and/or leucovorin calcium
- Active or uncontrolled infection
- Evidence of serious intercurrent illness (e.g., unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia)
- PRIOR CONCURRENT THERAPY:
- Recovered from all toxicities
- More than 4 weeks since prior major surgery
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- More than 2 weeks since completion of prior radiotherapy
- No prior radiotherapy to > 25% of bone marrow
- More than 2 week since prior cytotoxic chemotherapy, biologic therapy, or immunotherapy
- No concurrent sargramostim (GM-CSF)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pharmacogenetic-Based Phase I Trial of Irinotecan, 5-Fluorouracil, and Leucovorin (FOLFIRI) in Patients With Advanced Gastrointestinal Cancer
RATIONALE: Drugs used in chemotherapy, such as irinotecan, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when given together with fluorouracil and leucovorin in treating patients with advanced gastrointestinal cancer.
Read the detailed description
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of irinotecan hydrochloride in FOLFIRI for each respective UGT1A1 TA indel genotype grouping (group 1 [7/7, 7/8, 8/8], group 2 [6/7, 5/7, 5/8 ,6/8], and group 3 [6/6, 5/6, 5/5]).
Secondary
- Determine the molecular basis of toxicity, other than UGT1A1 variants, in FOLFIRI-treated cancer patients.
- Determine the pharmacodynamic molecular profiles of cell signaling pathways associated with the development and severity of early and late specific toxicities in cancer patients treated with FOLFIRI.
OUTLINE: This is a dose-escalation study of irinotecan hydrochloride. Patients are stratified according to genotype of UGT1A1 TA indel.
- Group 1 ( TA genotype 7/7, 7/8, 8/8): Patients receive irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV bolus over 5 minutes followed by IV continuously over 46 hours on days 1-3.
- Group 2 (TA genotype 6/7, 6/7, 5/8, 6/8): Patients receive treatment as in group 1 with a higher initial dose of irinotecan hydrochloride.
- Group 3 (TA genotype 5/5, 5/6, 6/6): Patients receive treatment as in group 2. In all groups, treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection at baseline and periodically during study for pharmacokinetics, dihydropyridine deaminase enzyme assay, and pathway expression analysis.
After completion of study treatment, patients are followed every 6 weeks for up to 2 years.
- Conditions
- Anal Cancer, Carcinoma of the Appendix, Colorectal Cancer, Esophageal Cancer, Extrahepatic Bile Duct Cancer, Gallbladder Cancer
- Being tested
- fluorouracil, irinotecan hydrochloride, leucovorin calcium, pharmacogenomic studies, pharmacological study
- Keywords
- stage IIIB anal cancer, stage IV anal cancer, recurrent anal cancer, carcinoma of the appendix, stage III colon cancer, stage IV colon cancer, recurrent colon cancer, stage III rectal cancer, stage IV rectal cancer, recurrent rectal cancer, stage III esophageal cancer, stage IV esophageal cancer, recurrent esophageal cancer, recurrent extrahepatic bile duct cancer, unresectable extrahepatic bile duct cancer, unresectable gallbladder cancer, recurrent gallbladder cancer, stage III gastric cancer, stage IV gastric cancer, recurrent gastric cancer
- Medical subject headings
- Anus Neoplasms, Appendiceal Neoplasms, Colorectal Neoplasms, Esophageal Neoplasms, Bile Duct Neoplasms, Gallbladder Neoplasms, Stomach Neoplasms, Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fluorouracilDrug
pharmacogenomic studiesOther
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of genotype-based dosing of FOLFIRI with or without monoclonal antibody therapy
Secondary outcomes (1)
Response rate of genotype-based dosing in the subset of patients that has colorectal cancer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2008 (estimated)
- Study startJun 2008
- Primary completionNov 2010
- Study completion3 Dec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anal CancerStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Robert McWilliams, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00654160
- Sponsor's protocol ID
- CDR0000592931
- Other IDs
- P30CA015083, MC064G, NCI-2009-01216
- Status last verified
- Sep 2016
- First submitted
- 4 Apr 2008
- Last updated
- 25 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacogenetic-Based Phase I Trial of Irinotecan, 5-Fluorouracil, and Leucovorin (FOLFIRI) in Patients With Advanced Gastrointestinal Cancer
- ClinicalTrials.gov ID
- NCT00654160
- Acronym / sponsor ID
- CDR0000592931
- Conditions
- Anal Cancer, Carcinoma of the Appendix, Colorectal Cancer, Esophageal Cancer, Extrahepatic Bile Duct Cancer, Gallbladder Cancer
- Keywords
- stage IIIB anal cancer, stage IV anal cancer, recurrent anal cancer, carcinoma of the appendix, stage III colon cancer, stage IV colon cancer, recurrent colon cancer, stage III rectal cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2008 (actual)
- Primary completion
- Nov 2010 (actual)
- Study completion
- 3 Dec 2012 (actual)
- First posted
- 7 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as irinotecan, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when given together with fluorouracil and leucovorin in treating patients with advanced gastrointestinal cancer.
Detailed description
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of irinotecan hydrochloride in FOLFIRI for each respective UGT1A1 TA indel genotype grouping (group 1 [7/7, 7/8, 8/8], group 2 [6/7, 5/7, 5/8 ,6/8], and group 3 [6/6, 5/6, 5/5]).
Secondary
- Determine the molecular basis of toxicity, other than UGT1A1 variants, in FOLFIRI-treated cancer patients.
- Determine the pharmacodynamic molecular profiles of cell signaling pathways associated with the development and severity of early and late specific toxicities in cancer patients treated with FOLFIRI.
OUTLINE: This is a dose-escalation study of irinotecan hydrochloride. Patients are stratified according to genotype of UGT1A1 TA indel.
- Group 1 ( TA genotype 7/7, 7/8, 8/8): Patients receive irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV bolus over 5 minutes followed by IV continuously over 46 hours on days 1-3.
- Group 2 (TA genotype 6/7, 6/7, 5/8, 6/8): Patients receive treatment as in group 1 with a higher initial dose of irinotecan hydrochloride.
- Group 3 (TA genotype 5/5, 5/6, 6/6): Patients receive treatment as in group 2. In all groups, treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection at baseline and periodically during study for pharmacokinetics, dihydropyridine deaminase enzyme assay, and pathway expression analysis.
After completion of study treatment, patients are followed every 6 weeks for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Life expectancy ≥ 12 weeks.
- ECOG performance status 0-2
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- SGOT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN if liver metastases)
Key exclusion criteria (10 listed)
- Known allergy to irinotecan hydrochloride-related agents (e.g., topotecan), 5-fluorouracil, and/or leucovorin calcium
- Active or uncontrolled infection
- Evidence of serious intercurrent illness (e.g., unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia)
- Recovered from all toxicities
- More than 4 weeks since prior major surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fluorouracil | Drug | – |
| irinotecan hydrochloride | Drug | – |
| leucovorin calcium | Drug | – |
| pharmacogenomic studies | Other | – |
| pharmacological study | Other | – |
Primary outcome
Maximum tolerated dose of genotype-based dosing of FOLFIRI with or without monoclonal antibody therapy
1 secondary outcome
Response rate of genotype-based dosing in the subset of patients that has colorectal cancer
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert McWilliams, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing fluorouracil, irinotecan hydrochloride and leucovorin calcium in people with Anal Cancer and Carcinoma of the Appendix, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose of genotype-based dosing of FOLFIRI with or without monoclonal antibody therapy. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2017.