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Adenocarcinoma of the RectumPhase 1NCT00052559

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

A Phase 1 study testing bevacizumab, fluorouracil and external beam radiation therapy in people with Adenocarcinoma of the Rectum and Stage II Rectal Cancer, run by National Cancer Institute (NCI) 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

This phase I trial is studying the side effects and best dose of bevacizumab when given together with fluorouracil and external-beam radiation therapy in treating patients with stage II or stage III rectal cancer. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
bevacizumab, fluorouracil and external beam radiation therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
2 sitesUnited States
Study dates
Aug 2002to Apr 2003
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

Who may be able to join

  • Histologically confirmed primary adenocarcinoma of the rectum that begins within 15 cm of the anal verge as determined by sigmoidoscopy and/or colonoscopy
  • Clinical T3 or T4 tumors as determined by the following features:
  • Tethered or fixed tumor on physical exam
  • cT3, cT4, or N+ disease must be confirmed by an endorectal ultrasound or surface coil MRI
  • There must be no evidence of metastatic disease as confirmed by physical examination, chest radiograph, and abdominal/pelvic CT scan
  • ECOG performance status 0, 1, 2 (Karnofsky >= 70%)
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  • Life expectancy of greater than 2 years
  • Leukocytes >= 3,000/ul
  • Absolute neutrophil count >= 1,500/ul
  • Platelets >= 100,000/ul
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • The effects of bevacizumab on the developing human fetus are unknown; for this reason and because radiation therapy and 5-FU agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients with no known HIV or HIV risk factors will be eligible for this study without HIV testing

Who cannot join

  • Patients with a "concurrently active" second malignancy other than non- melanoma skin cancers or in situ cervical cancer are excluded; patients are not considered to have a "concurrently active" malignancy if they have completed therapy and considered by their physician to be at less than 30% risk of relapse at a minimum of 5 years after all therapy
  • Prior Treatment:
  • No prior treatment for this malignancy
  • No prior history of pelvic irradiation
  • No prior history of 5-FU-based therapy for any malignancy
  • No prior treatment with bevacizumab
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  • Patients must not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition bevacizumab or other agents used in study
  • Bevacizumab - Specific exclusion criteria:
  • History or evidence upon physical examination of CNS disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of stroke
  • Serious, non-healing wound, ulcer, or bone fracture
  • Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, history of myocardial infarction, unstable angina within 12 months), New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or Grade II or greater peripheral vascular disease within 1 year prior to Day 0
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study; biopsies (other than rectal cancer) within 7 days prior to Day 0; placement of a vascular access device within 7 days prior to Day 0
  • Arterial thromboembolic events within previous 12 months including transient ischemic attack, cerebrovascular accident, unstable angina, myocardial infarction, or clinically significant peripheral vascular disease. Vascular surgery, stenting or angioplasty within previous 12 months; no history of venous thromboembolic events that require continuation of therapeutic dose of anticoagulation
  • Current or recent (within 10 days prior to Day 0) use of full-dose oral or parenteral anticoagulants or thrombolytic agents (except as required to maintain patency of preexisting, permanent indwelling IV catheters; for subjects receiving warfarin, international normalized ratio [INR] of < 1.5; appropriate use of heparin should be discussed with the Medical Monitor)
  • Chronic, daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti- inflammatory medications (of the kind known to inhibit platelet function at doses used to treat chronic inflammatory diseases)
  • Presence of bleeding diathesis or coagulopathy
  • Active infection requiring parenteral antibiotics on Day 0
  • Proteinuria at baseline or clinically significant impairment of renal function
  • Subjects unexpectedly discovered to have >= 1+ proteinuria during screening should undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate < 1 gram protein/24 hr to allow participation in the study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because bevacizumab, radiation therapy, and 5-FU have potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with bevacizumab, breastfeeding should be discontinued if the mother is treated with bevacizumab; these potential risks may also apply to other agents used in this study

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: A Phase I Study Of The Antiangiogenic Agent Bevacizumab In Combination With 5-Fluourouracil And External Beam Radiation Therapy In Rectal Cancer

This phase I trial is studying the side effects and best dose of bevacizumab when given together with fluorouracil and external-beam radiation therapy in treating patients with stage II or stage III rectal cancer. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining monoclonal antibody therapy with chemotherapy and radiation therapy may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of a vascular endothelial growth factor (VEGF) neutralizing antibody, bevacizumab, when administered concurrently with 5-fluorouracil (5-FU) and external beam radiation therapy (EBRT) in patients with clinical stage T3 or T4 rectal cancer prior to surgery.

II. To obtain preliminary data of the pathological response rate after preoperative therapy.

III. To obtain preliminary data regarding progression free survival, local control, and overall survival.

IV. To obtain preliminary data of the changes in the angiogenic profile of rectal cancer induced by this therapy.

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

Patients receive bevacizumab IV over 30-90 minutes on day 1 (courses 1-4). Beginning with course 2, patients also receive fluorouracil IV continuously on days 1-14 and undergo external beam radiotherapy on days 1-5 and 8-12. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo surgery 7 weeks after completion of chemoradiotherapy.

Cohorts of 6 patients receive escalating doses of bevacizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 20 additional patients are treated at the MTD.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 2 years.

Being tested
bevacizumab, fluorouracil, external beam radiation therapy, therapeutic conventional surgery, laboratory biomarker analysis
Medical subject headings
Rectal Neoplasms

What participants receive

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

  • bevacizumabBiological

    Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

    Given IV

  • fluorouracilDrug

    Also called 5-fluorouracil, 5-Fluracil, 5-FU

    Given IV

  • external beam radiation therapyRadiation

    Also called EBRT

    Undergo external beam radiation therapy

  • therapeutic conventional surgeryProcedure or surgery

    Undergo surgery

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00052559
Study groupRoleWhat they receive
Treatment (bevacizumab, fluorouracil, radiation therapy)ExperimentalPatients receive bevacizumab IV over 30-90 minutes on day 1 (courses 1-4). Beginning with course 2, patients also receive fluorouracil IV continuously on days 1-14 and undergo external beam radiotherapy on days 1-5 and 8-12. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo surgery 7 weeks after completion of chemoradiotherapy. Cohorts of 6 patients receive escalating doses of bevacizumab until the MTD is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 20 additional patients are treated at the MTD.
Receives: Biological: bevacizumab; Drug: fluorouracil; Radiation: external beam radiation therapy; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis

What is being measured

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

  1. Maximum tolerated dose of bevacizumab when administered concurrently with 5-fluorouracil (5-FU) and external beam radiation therapy (EBRT) in patients with cT3 and T4 rectal cancer prior to surgery

    Measured: 29 days

Secondary outcomes (4)

  1. Pathological response rate after preoperative bevacizumab, 5-FU, EBRT, and surgery

    Measured: Up to 5 years

  2. Progression-free survival

    The progression-free survival curve will be estimated using the Kaplan-Meier methods.

    Measured: From protocol entry until documented progression of disease or death from any cause, assessed up to 5 years

  3. Local control

    Measured: Up to 5 years

  4. Overall survival

    Measured: Up to 5 years

Timeline

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

  1. First posted27 Jan 2003 (estimated)
  2. Study startAug 2002
  3. Primary completionApr 2003

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
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00052559
Sponsor's protocol ID
NCI-2012-02908
Other IDs
6042-05-7R1, CDR0000258532, U01CA099118, U01CA062490
Status last verified
Jun 2013
First submitted
24 Jan 2003
Last updated
5 Jun 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing bevacizumab, fluorouracil and external beam radiation therapy in people with Adenocarcinoma of the Rectum and Stage II Rectal Cancer, run by National Cancer Institute (NCI) 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?

The sponsor lists 16 inclusion and 22 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 5 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 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 of bevacizumab when administered concurrently with 5-fluorouracil (5-FU) and external beam radiation therapy (EBRT) in patients with cT3 and T4 rectal cancer prior to surgery (time frame: 29 days). 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 NCT00052559.

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 5 Jun 2013.

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