Colorectal CancerPhase 1NCT01164215
Biomarker-Guided Fluorouracil in Treating Patients With Colorectal Cancer Receiving Combination Chemotherapy
A Phase 1 study testing fluorouracil, leucovorin and oxaliplatin in people with Colorectal Cancer and Diarrhea, run by UNC Lineberger Comprehensive Cancer Center at 5 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, and leucovorin calcium, 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?
- Any age
- Conditions the study is for
- Colorectal Cancer, Diarrhea, Neutropenia
- What is being tested?
- fluorouracil, leucovorin and oxaliplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 5 sitesUnited States
- Study dates
- Feb 2010to Sep 2013
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed colorectal cancer
- Patients scheduled to receive mFOLFOX6 (in the adjuvant setting or for metastatic disease) as part of their chemotherapy regimen
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy > 6 months
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Serum creatinine ≤ 1.5 mg/dL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)
- Fertile patients must use effective contraception
- Negative pregnancy test
- Not pregnant or nursing
- No serious concomitant systemic disorders, including active infection that, in the opinion of the investigator, would compromise the patient's safety or ability to complete the study
- No altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
- Must be able to follow protocol requirements and give informed consent
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Concurrent bevacizumab allowed
- No concurrent warfarin (Coumadin®)
- Concurrent enoxaparin (Lovenox®) allowed
- No concurrent theophylline or aminophylline
- No chocolate beginning 12 hours before day 1 of each course and through the end of that course's fluorouracil continuous IV
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Cancer Care of Western North Carolina
Asheville, North Carolina, 28801
Moses Cone Regional Cancer Center at Wesley Long Community Hospital
Greensboro, North Carolina, 27403-1198
Leo W. Jenkins Cancer Center at ECU Medical School
Greenville, North Carolina, 27834
Rex Cancer Center at Rex Hospital
Raleigh, North Carolina, 27607
Marion L. Shepard Cancer Center
Washington, North Carolina, 27889
About this study
Official title: Multicenter Study Investigating Utilization of Pharmacokinetic-Guided 5-Fluorouracil in Patients Receiving mFOLFOX6 With or Without Bevacizumab
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, and leucovorin calcium, 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. Studying samples of blood in the laboratory from patients with cancer receiving fluorouracil in combination with oxaliplatin and leucovorin calcium may help doctors learn how fluorouracil works in the body and how patients will respond to treatment.
PURPOSE: This phase I trial is studying biomarker-guided fluorouracil in treating patients with colorectal cancer receiving combination chemotherapy.
Read the detailed description
OBJECTIVES:
Primary
- To determine whether 4 courses of pharmacokinetic (PK)-guided 5-fluorouracil chemotherapy improves the ability to achieve a targeted area under the curve (20 to 25 mg*hr/L) in patients with colorectal cancer receiving mFOLFOX6 chemotherapy as compared to historical non-PK-guided therapy in patients treated with a similar FOLFOX regimen.
Secondary
- To determine and compare the incidence of neutropenia and diarrhea in patients treated with these regimens.
OUTLINE: This is a multicenter study.
- Standard mFOLFOX6 (course 1): Patients receive fluorouracil IV bolus over 1-5 minutes followed by fluorouracil IV continuously over 46 hours, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1.
Patients undergo plasma sample collection periodically during study for pharmacokinetic (PK)-guided fluorouracil dose determination for courses 2-4.
- PK-guided mFOLFOX6 (courses 2-4): Patients receive fluorouracil bolus, oxaliplatin, and leucovorin calcium as in course 1. Patients also receive fluorouracil* IV continuously as determined by the PK-guided analysis.
NOTE: *The continuous infusion fluorouracil dose adjustment is calculated based on the results of PK plasma concentrations and the corresponding AUC from the preceding course.
- Conditions
- Colorectal Cancer, Diarrhea, Neutropenia
- Being tested
- fluorouracil, leucovorin, oxaliplatin
- Keywords
- neutropenia, diarrhea, stage I colon cancer, stage II colon cancer, stage III colon cancer, stage IV colon cancer, recurrent colon cancer, stage I rectal cancer, stage II rectal cancer, stage III rectal cancer, stage IV rectal cancer, recurrent rectal cancer
- Medical subject headings
- Colorectal Neoplasms, Diarrhea, Neutropenia, Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fluorouracilDrug
Also called 5FU
200-400 mg/m2 intravenously, 1 -5 minutes, once every 2 weeks 2400 mg/m2 intravenously over a period of 46 hours, once every 2 weeks
leucovorinDrug
Also called leucovorin calcium
200-400 mg/m2, intravenously over a period of 2 hours, once every 2 weeks
oxaliplatinDrug
Also called Eloxatin
85 mg/m2, intravenously for 2 hours, once every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| mFOLFOX6 | Experimental | Patients will receive cycle 1 of standard dose mFOLFOX6, with the same dose of mFOLFOX6 continued in subsequent cycles, once patient achieves the target AUC.
mFOLFOX 6 is a regimen comprised of Oxaliplatin + Leucovorin +5-Fluorouracil (FU) Receives: Drug: fluorouracil; Drug: leucovorin; Drug: oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Achievement of targeted AUC using pharmacokinetic (PK)-guided 5 fluorouracil as part of mFOLFOX6 therapy
Measured: During first 4 cycles of drug therapy
Secondary outcomes (1)
Toxicity differences between PK-guided therapy versus non-PK-guided therapy
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2010 (estimated)
- Study startFeb 2010
- Primary completionNov 2012
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Christine M. Walko, PharmD, BCOP, Principal investigator, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01164215
- Sponsor's protocol ID
- LCCC 0918
- Other IDs
- P30CA016086, CDR0000681338
- Status last verified
- Oct 2015
- First submitted
- 15 Jul 2010
- Last updated
- 9 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Williams GR, Deal AM, Shachar SS, Walko CM, Patel JN, O'Neil B, McLeod HL, Weinberg MS, Choi SK, Muss HB, Sanoff HK. The impact of skeletal muscle on the pharmacokinetics and toxicity of 5-fluorouracil in colorectal cancer. Cancer Chemother Pharmacol. 2018 Feb;81(2):413-417. doi: 10.1007/s00280-017-3487-2. Epub 2017 Nov 20.
PubMed 29159476Patel JN, O'Neil BH, Deal AM, Ibrahim JG, Sherrill GB, Olajide OA, Atluri PM, Inzerillo JJ, Chay CH, McLeod HL, Walko CM. A community-based multicenter trial of pharmacokinetically guided 5-fluorouracil dosing for personalized colorectal cancer therapy. Oncologist. 2014 Sep;19(9):959-65. doi: 10.1634/theoncologist.2014-0132. Epub 2014 Aug 12.
PubMed 25117066
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Study Investigating Utilization of Pharmacokinetic-Guided 5-Fluorouracil in Patients Receiving mFOLFOX6 With or Without Bevacizumab
- ClinicalTrials.gov ID
- NCT01164215
- Acronym / sponsor ID
- LCCC 0918
- Conditions
- Colorectal Cancer, Diarrhea, Neutropenia
- Keywords
- neutropenia, diarrhea, stage I colon cancer, stage II colon cancer, stage III colon cancer, stage IV colon cancer, recurrent colon cancer, stage I rectal cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2010
- Primary completion
- Nov 2012 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 16 Jul 2010 (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 fluorouracil, oxaliplatin, and leucovorin calcium, 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. Studying samples of blood in the laboratory from patients with cancer receiving fluorouracil in combination with oxaliplatin and leucovorin calcium may help doctors learn how fluorouracil works in the body and how patients will respond to treatment.
PURPOSE: This phase I trial is studying biomarker-guided fluorouracil in treating patients with colorectal cancer receiving combination chemotherapy.
Detailed description
OBJECTIVES:
Primary
- To determine whether 4 courses of pharmacokinetic (PK)-guided 5-fluorouracil chemotherapy improves the ability to achieve a targeted area under the curve (20 to 25 mg*hr/L) in patients with colorectal cancer receiving mFOLFOX6 chemotherapy as compared to historical non-PK-guided therapy in patients treated with a similar FOLFOX regimen.
Secondary
- To determine and compare the incidence of neutropenia and diarrhea in patients treated with these regimens.
OUTLINE: This is a multicenter study.
- Standard mFOLFOX6 (course 1): Patients receive fluorouracil IV bolus over 1-5 minutes followed by fluorouracil IV continuously over 46 hours, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1.
Patients undergo plasma sample collection periodically during study for pharmacokinetic (PK)-guided fluorouracil dose determination for courses 2-4.
- PK-guided mFOLFOX6 (courses 2-4): Patients receive fluorouracil bolus, oxaliplatin, and leucovorin calcium as in course 1. Patients also receive fluorouracil* IV continuously as determined by the PK-guided analysis.
NOTE: *The continuous infusion fluorouracil dose adjustment is calculated based on the results of PK plasma concentrations and the corresponding AUC from the preceding course.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| mFOLFOX6 | Experimental | Drug: fluorouracil, Drug: leucovorin, Drug: oxaliplatinPatients will receive cycle 1 of standard dose mFOLFOX6, with the same dose of mFOLFOX6 continued in subsequent cycles, once patient achieves the target AUC. mFOLFOX 6 is a regimen comprised of Oxaliplatin + Leucovorin +5-Fluorouracil (FU) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 |
|---|---|---|
| fluorouracilAlso: 5FU200-400 mg/m2 intravenously, 1 -5 minutes, once every 2 weeks 2400 mg/m2 intravenously over a period of 46 hours, once every 2 weeks | Drug | mFOLFOX6 |
| leucovorinAlso: leucovorin calcium200-400 mg/m2, intravenously over a period of 2 hours, once every 2 weeks | Drug | mFOLFOX6 |
| oxaliplatinAlso: Eloxatin85 mg/m2, intravenously for 2 hours, once every 2 weeks | Drug | mFOLFOX6 |
Primary outcome
Achievement of targeted AUC using pharmacokinetic (PK)-guided 5 fluorouracil as part of mFOLFOX6 therapy
Time frame: During first 4 cycles of drug therapy
1 secondary outcome
Toxicity differences between PK-guided therapy versus non-PK-guided therapy
Time frame: 24 months
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 9 Oct 2015.
- Derived from this study: PubMed 29159476Williams GR, Deal AM, Shachar SS, Walko CM, Patel JN, O'Neil B, McLeod HL, Weinberg MS, Choi SK, Muss HB, Sanoff HK. The impact of skeletal muscle on the pharmacokinetics and toxicity of 5-fluorouracil in colorectal cancer. Cancer Chemother Pharmacol. 2018 Feb;81(2):413-417. doi: 10.1007/s00280-017-3487-2. Epub 2017 Nov 20.
- Derived from this study: PubMed 25117066Patel JN, O'Neil BH, Deal AM, Ibrahim JG, Sherrill GB, Olajide OA, Atluri PM, Inzerillo JJ, Chay CH, McLeod HL, Walko CM. A community-based multicenter trial of pharmacokinetically guided 5-fluorouracil dosing for personalized colorectal cancer therapy. Oncologist. 2014 Sep;19(9):959-65. doi: 10.1634/theoncologist.2014-0132. Epub 2014 Aug 12.
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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.
Christine M. Walko, PharmD, BCOP principal investigator
UNC Lineberger Comprehensive Cancer Center
5 sites 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, leucovorin and oxaliplatin in people with Colorectal Cancer and Diarrhea, run by UNC Lineberger Comprehensive Cancer Center at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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?
Achievement of targeted AUC using pharmacokinetic (PK)-guided 5 fluorouracil as part of mFOLFOX6 therapy (time frame: During first 4 cycles of drug therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01164215, which also lists 2 linked publications.
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 9 Oct 2015.