Colorectal CancerPhase 1NCT00098982
Bortezomib, Fluorouracil, Leucovorin, and Oxaliplatin in Treating Patients With Advanced or Metastatic Colorectal Cancer
A Phase 1 study testing bortezomib, fluorouracil and leucovorin calcium in people with Colorectal Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 3 sites in 3 countries.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- bortezomib, fluorouracil and leucovorin calcium
- How many people
- 16 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Sep 2004to Jan 2007
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed advanced or metastatic colorectal cancer
- Amenable to first-line treatment with oxaliplatin, fluorouracil, and leucovorin calcium for advanced or metastatic disease
- No symptomatic or radiologic evidence of brain metastases
PATIENT CHARACTERISTICS:
Age
- Over 18
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 2,000/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
- AST and ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
Renal
- Creatinine ≤ 1.7 mg/dL
Cardiovascular
- No ischemic heart disease within the past 6 months
- No clinically significant ECG changes
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No baseline neuropathy > grade 1
- No other prior or concurrent malignancy except cone-biopsied carcinoma of the cervix or adequately treated basal cell or squamous cell skin cancer
- No unstable systemic disease
- No active uncontrolled infection
- No psychological, familial, sociological, or geographical condition that would preclude study participation
- No hypersensitivity to bortezomib, boron, or mannitol
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No prior oxaliplatin
- No prior chemotherapy for advanced or metastatic disease
- At least 6 months since prior adjuvant chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- More than 4 weeks since prior radiotherapy
Surgery
- More than 14 days since prior major surgery
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
Switzerland1 site
Centre Hospitalier Universitaire Vaudois
Lausanne, CH-1011
United Kingdom1 site
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, LS9 7TF
About this study
Official title: Phase I Study of PS-341 (VELCADE) in Combination With 5FU/LV Plus Oxaliplatin in Patients With Advanced Colorectal Cancer
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also help the chemotherapy drugs work better by making tumor cells more sensitive to the drugs. Giving bortezomib with fluorouracil, leucovorin, and oxaliplatin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given with fluorouracil, leucovorin, and oxaliplatin in treating patients with advanced or metastatic colorectal cancer.
Read the detailed description
OBJECTIVES:
Primary
- Determine the dose-limiting toxicity and maximum tolerated dose of bortezomib when administered with fluorouracil, leucovorin calcium, and oxaliplatin in patients with advanced or metastatic colorectal cancer.
- Determine the recommended phase II dose of bortezomib in patients treated with this regimen.
Secondary
- Determine response in patients with measurable disease treated with this regimen.
OUTLINE: This is an open-label, non-randomized, multicenter, dose-escalation study of bortezomib.
Patients receive bortezomib IV over 3-5 seconds on days 1, 8, and 15; oxaliplatin IV over 2 hours on days 1 and 15; and leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 1, 2, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Additional patients receive treatment at the MTD to a maximum of 12 patients at that dose level.
Patients are followed every 8 weeks until disease progression or start of a new anticancer treatment.
PROJECTED ACCRUAL: Not specified.
- Conditions
- Colorectal Cancer
- Being tested
- bortezomib, fluorouracil, leucovorin calcium, oxaliplatin
- Keywords
- stage III colon cancer, stage IV colon cancer, stage III rectal cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
fluorouracilDrug
oxaliplatinDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose and recommended dose of bortezomib as measured by CTC v3.0
Secondary outcomes (3)
Safety as measured by CTC v3.0
Response as measured by RECIST every 8 weeks
Time to progression as measured by Kaplan Meier and RECIST every 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2004 (estimated)
- Study startSep 2004
- Primary completionJan 2007
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 European Organisation for Research and Treatment of Cancer - EORTCThe 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
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Francesco Caponigro, MD, Study chair, Istituto Nazionale per lo Studio e la Cura dei Tumori
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00098982
- Sponsor's protocol ID
- EORTC-16029
- Other IDs
- EORTC-16029, MILLENNIUM-EORTC-16029, 2004-001763-21, 2004
- Status last verified
- Jun 2013
- First submitted
- 8 Dec 2004
- Last updated
- 12 Jun 2013
- Results posted
- No
Publications
Caponigro F, Lacombe D, Twelves C, Bauer J, Govaerts AS, Marreaud S, Milano A, Anthoney A. An EORTC phase I study of Bortezomib in combination with oxaliplatin, leucovorin and 5-fluorouracil in patients with advanced colorectal cancer. Eur J Cancer. 2009 Jan;45(1):48-55. doi: 10.1016/j.ejca.2008.08.011. Epub 2008 Sep 20.
PubMed 18809314Lacombe DA, Caponigro F, Anthoney A, et al.: A phase I study of bortezomib in combination with 5FU/LV plus oxaliplatin in patients (pts) with advanced colorectal cancer (CRC): EORTC 16029. [Abstract] J Clin Oncol 25 (Suppl 18): A-4090, 2007.
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of PS-341 (VELCADE) in Combination With 5FU/LV Plus Oxaliplatin in Patients With Advanced Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00098982
- Acronym / sponsor ID
- EORTC-16029
- Conditions
- Colorectal Cancer
- Keywords
- stage III colon cancer, stage IV colon cancer, stage III rectal cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Study start
- Sep 2004
- Primary completion
- Jan 2007 (actual)
- First posted
- 9 Dec 2004 (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, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also help the chemotherapy drugs work better by making tumor cells more sensitive to the drugs. Giving bortezomib with fluorouracil, leucovorin, and oxaliplatin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given with fluorouracil, leucovorin, and oxaliplatin in treating patients with advanced or metastatic colorectal cancer.
Detailed description
OBJECTIVES:
Primary
- Determine the dose-limiting toxicity and maximum tolerated dose of bortezomib when administered with fluorouracil, leucovorin calcium, and oxaliplatin in patients with advanced or metastatic colorectal cancer.
- Determine the recommended phase II dose of bortezomib in patients treated with this regimen.
Secondary
- Determine response in patients with measurable disease treated with this regimen.
OUTLINE: This is an open-label, non-randomized, multicenter, dose-escalation study of bortezomib.
Patients receive bortezomib IV over 3-5 seconds on days 1, 8, and 15; oxaliplatin IV over 2 hours on days 1 and 15; and leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 1, 2, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Additional patients receive treatment at the MTD to a maximum of 12 patients at that dose level.
Patients are followed every 8 weeks until disease progression or start of a new anticancer treatment.
PROJECTED ACCRUAL: Not specified.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- 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 |
|---|---|---|
| bortezomib | Drug | – |
| fluorouracil | Drug | – |
| leucovorin calcium | Drug | – |
| oxaliplatin | Drug | – |
Primary outcome
Maximum tolerated dose and recommended dose of bortezomib as measured by CTC v3.0
3 secondary outcomes
Safety as measured by CTC v3.0
Response as measured by RECIST every 8 weeks
Time to progression as measured by Kaplan Meier and RECIST every 8 weeks
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 12 Jun 2013.
- Results publication: PubMed 18809314Caponigro F, Lacombe D, Twelves C, Bauer J, Govaerts AS, Marreaud S, Milano A, Anthoney A. An EORTC phase I study of Bortezomib in combination with oxaliplatin, leucovorin and 5-fluorouracil in patients with advanced colorectal cancer. Eur J Cancer. 2009 Jan;45(1):48-55. doi: 10.1016/j.ejca.2008.08.011. Epub 2008 Sep 20.
- Results publicationLacombe DA, Caponigro F, Anthoney A, et al.: A phase I study of bortezomib in combination with 5FU/LV plus oxaliplatin in patients (pts) with advanced colorectal cancer (CRC): EORTC 16029. [Abstract] J Clin Oncol 25 (Suppl 18): A-4090, 2007.
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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.
Francesco Caponigro, MD study chair
Istituto Nazionale per lo Studio e la Cura dei Tumori
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bortezomib, fluorouracil and leucovorin calcium in people with Colorectal Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 12 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy, Switzerland, United Kingdom. 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 and recommended dose of bortezomib as measured by CTC v3.0. 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 NCT00098982, 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 12 Jun 2013.