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Colorectal CancerPhase 1NCT00280176

Bortezomib, Fluorouracil, and External-Beam Radiation Therapy in Treating Patients With Stage II, Stage III, or Stage IV Rectal Cancer

A Phase 1 study testing bortezomib, fluorouracil and radiation therapy in people with Colorectal Cancer, run by UNC Lineberger Comprehensive Cancer Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from… 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 radiation therapy
Type of treatment
Surgery or procedure
How many people
11 participants
Where
2 sitesUnited States
Study dates
Apr 2003to Sep 2010
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:

  • Biopsy confirmed diagnosis of adenocarcinoma of the rectum meeting 1 of the following clinical staging criteria:
  • T3-T4, N0, M0 (stage II disease)
  • T4 disease defined as tumor fixed on examination or involving adjacent pelvic structures, such as the sidewall, bladder, uterus, prostate, or small bowel by ultrasound or CT scan
  • Any T, N1-2, M0 (stage III disease)
  • Any T, any N, M1 (stage IV disease)
  • Recurrent disease (any prior stage)
  • Candidate for local palliative therapy or curative resection of metastatic disease
  • Previously treated CNS disease allowed provided it is stable for > 3 months

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy > 3 months
  • Adequate nutrition
  • WBC ≥ 4,000/mm³
  • ANC > 2,000/mm³
  • Platelet count ≥ 100,000/mm³
  • Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 30 mL/min
  • Bilirubin ≤ 1.5 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No serious medical or psychiatric illness that would limit study compliance or limit survival to < 2 years
  • No history of refractory congestive heart failure or cardiomyopathy
  • No active coronary artery disease, myocardial infarction within the past 3 months, or cerebrovascular accident within the past 3 months
  • No peripheral neuropathy ≥ grade 2
  • No hypersensitivity to bortezomib, boron, or mannitol

PRIOR CONCURRENT THERAPY:

  • More than 1 week since prior major surgery
  • More than 28 days since prior investigational agents
  • Prior chemotherapy allowed
  • No prior pelvic radiotherapy (for treatment of any pelvic malignancy)
  • No concurrent herbal medication (excluding vitamin and mineral supplements)
  • No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

    Chapel Hill, North Carolina, 27599-7295

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232-6838

Other trials in United States

About this study

Official title: Phase I Study of PS-341 in Combination With 5-Fluorouracil and External Beam Radiotherapy For The Treatment Of Locally Advanced And Metastatic Rectal Cancer

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bortezomib and fluorouracil together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with fluorouracil and external-beam radiation therapy in treating patients with stage II, stage III, or stage IV rectal cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of bortezomib when administered in combination with fluorouracil and external beam radiotherapy as preoperative or palliative treatment in patients with stage II-IV rectal adenocarcinoma.
  • Determine the dose-limiting toxicities of this regimen in these patients.

Secondary

  • Determine the dose-effect relationship of bortezomib on NF-kappa B activation induced by chemoradiotherapy.
  • Determine downstream events induced by NF-kappa B activation.
  • Determine downstream events related to activation of p53 in response to treatment with chemoradiotherapy and bortezomib.
  • Determine the rate of complete pathologic remission in patients who undergo surgical resection of their primary tumor.
  • Determine the gene expression pattern of tumors by cDNA microarray analysis before and during treatment with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of bortezomib.

Patients receive bortezomib IV on days 1, 4, 8, 11, 22, 25, 29, and 32 and fluorouracil IV continuously on days 2-38. Patients also undergo external beam radiotherapy 5 days a week for 5½ weeks. Treatment continues 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.

Patients undergo tissue biopsy at baseline and on days 1 and 2. Samples are collected and evaluated by tissue microarray analysis for NF-kappa B pathway activation; cDNA analysis, RNase protection assay, and immunohistochemistry for analysis of downstream events induced by NF-kappa B activation; and modified TdT-mediated dUTP nick-end label for analysis of apoptosis by DNA fragmentation. NF-kappa B subunits are quantified by enzyme-linked immunosorbent assay. Serum samples are collected at baseline and stored for future studies.

After completion of study treatment, patients are followed every 3 months for up to 2 years.

Being tested
bortezomib, fluorouracil, radiation therapy
Keywords
recurrent rectal cancer, stage II rectal cancer, stage III rectal cancer, stage IV rectal cancer, adenocarcinoma of the rectum
Medical subject headings
Colorectal Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bortezomibDrug

    Also called Velcade

    0.7mg/m2 - 1.5mg.m2 given during Weeks 1, 2, 4 and 5 on a Monday/Thursday or Tuesday/Friday schedule, up to six weeks

  • fluorouracilDrug

    Also called 5FU

    225mg/m2 given weekly, up to 6 weeks

  • radiation therapyRadiation

    180 cGy, every 5 days, up to six weeks

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose

    Measured: 6 weeks

  2. Dose-limiting toxicity

    Measured: 8 weeks

Secondary outcomes (5)

  1. Dose-effect relationship of bortezomib on NF-kappa B activation induced by chemoradiotherapy

    Measured: 6 weeks

  2. Downstream events induced by NF-kappa B activation

    Measured: 8 weeks

  3. Downstream events related to activation of p53 in response to treatment with chemoradiotherapy and bortezomib

    Measured: 8 weeks

  4. Rate of complete pathologic remission

    Measured: 2 years

  5. Gene expression pattern of tumors as assessed by cDNA microarray analysis pre- and post-treatment

    Measured: 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2006 (estimated)
  2. Study startApr 2003
  3. Primary completionNov 2008
  4. Study completionSep 2010

Resources

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
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00280176
Sponsor's protocol ID
LCCC 0209
Other IDs
CDR0000549844
Status last verified
Feb 2012
First submitted
18 Jan 2006
Last updated
14 Feb 2012
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing bortezomib, fluorouracil and radiation therapy in people with Colorectal Cancer, run by UNC Lineberger Comprehensive Cancer Center at 2 sites 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?

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 14 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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?

Maximum tolerated dose (time frame: 6 weeks). The study lists 2 primary outcomes in all. 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 NCT00280176.

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 14 Feb 2012.

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