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Recurrent Colon CancerPhase 2NCT00077298

Bevacizumab and Cetuximab With or Without Irinotecan in Treating Patients With Irinotecan-Refractory Metastatic Colorectal Cancer

A Phase 2 study testing cetuximab, bevacizumab and irinotecan hydrochloride in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, run by National Cancer Institute (NCI) at 1 site 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 randomized phase II trial is studying giving bevacizumab and cetuximab together with irinotecan to see how well it works compared to giving bevacizumab and cetuximab alone in treating patients with irinotecan-refractory metastatic colorectal cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
cetuximab, bevacizumab and irinotecan hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteUnited States
Study dates
Dec 2003to Jul 2007
Phase
Phase 2
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 or cytologically confirmed colorectal cancer
  • Metastatic disease by diagnostic imaging studies
  • Measurable disease
  • At least 1 unidimensionally measurable lesion with minimum lesion size at least twice the slice thickness of the imaging study used
  • Refractory to irinotecan, evidenced by clinical documentation
  • Received at least 1 prior irinotecan-containing chemotherapy regimen for metastatic disease and progressed during or within 6 weeks after completion of therapy
Show all 69Show fewer
  • Must have received prior irinotecan according to 1 of the following schedules:
  • Weekly administration with a starting dose of 100-125 mg/m^2
  • Biweekly administration (every other week) with a starting dose of approximately 180 mg/m^2
  • Once every three weekly administration with a starting dose of 300-350 mg/m^2
  • No known brain metastases
  • No prior primary CNS tumors
  • Performance status - ECOG 0-1
  • Performance status - Karnofsky 80-100%
  • More than 3 months
  • WBC >= 3,000/mm^3
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 9 g/dL
  • No bleeding diathesis or coagulopathy
  • Bilirubin normal
  • AST and ALT =< 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of known liver metastases)
  • INR < 1.5 (for patients receiving warfarin)
  • Creatinine =< ULN
  • Creatinine clearance ≥ 60 mL/min
  • No proteinuria
  • No prior stroke
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No uncontrolled hypertension
  • No clinically significant cardiac arrhythmia
  • None of the following arterial thromboembolic events within the past 6 months:
  • Myocardial infarction
  • Cerebrovascular accident
  • Transient ischemic attack
  • Unstable angina
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 3 months after study participation
  • No significant traumatic injury within the past 28 days
  • No grade 3 or greater neurotoxicity
  • No uncontrolled seizures
  • No prior allergic reactions attributed to compounds of similar chemical or biological composition to study agents
  • No prior irinotecan intolerance
  • No ongoing or active infection requiring parenteral antibiotics
  • No serious nonhealing active wound, ulcer, or bone fracture
  • No psychiatric illness or social situation that would preclude study compliance
  • No other concurrent uncontrolled illness that would preclude study participation
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No prior cetuximab
  • No other prior epidermal growth factor receptor-directed therapy
  • No prior anticancer murine or chimeric monoclonal antibody therapy
  • Prior humanized monoclonal antibody therapy allowed
  • No prior bevacizumab
  • No other prior vascular endothelial growth factor-targeted therapy
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • More than 4 weeks since prior radiotherapy
  • More than 28 days since prior major surgical procedure or open biopsy
  • Recovered from all prior therapy
  • Any number of prior standard or investigational regimens allowed
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  • No recent or concurrent thrombolytic agents
  • No recent or concurrent full-dose warfarin except as required to maintain patency of preexisting, permanent indwelling IV catheters
  • No concurrent therapeutic heparin
  • Concurrent prophylactic low-molecular weight heparin allowed
  • No concurrent chronic daily aspirin (> 325 mg/day)
  • No concurrent nonsteroidal anti-inflammatory medications known to inhibit platelet function
  • No concurrent combination antiretroviral therapy for HIV-positive patients

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Randomized Phase II Study of Bevacizumab in Combination With Cetuximab Plus Irinotecan, or in Combination With Cetuximab Alone, in Irinotecan-Refractory Colorectal Cancer

This randomized phase II trial is studying giving bevacizumab and cetuximab together with irinotecan to see how well it works compared to giving bevacizumab and cetuximab alone in treating patients with irinotecan-refractory metastatic colorectal cancer. Monoclonal antibodies such as cetuximab and bevacizumab can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or deliver tumor -killing substances to them. Drugs used in chemotherapy, such as irinotecan, also work in different ways to kill tumor cells or stop them from growing. Giving cetuximab and bevacizumab together with irinotecan may improve the ability to block tumor growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Evaluate time to tumor progression in patients with irinotecan-refractory metastatic colorectal cancer treated with bevacizumab and cetuximab with or without irinotecan.

II. Evaluate objective response rate in patients treated with these regimens. III. Evaluate overall survival of patients treated with these regimens. IV. Evaluate safety, tolerability, and adverse event profiles of these regimens in these patients.

  1. Correlate a panel of molecular markers (e.g., those involved in the epidermal growth factor receptor signaling pathway, angiogenic pathway, and irinotecan metabolism) with clinical outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, ECOG performance status (0 vs 1), and albumin (> 3.0 g/dL vs ≤ 3.0 g/dL). Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36; bevacizumab IV over 30-90 minutes on days 1*, 15, and 29 OR on days 1 and 22; and irinotecan IV over 30-90 minutes (at the same dose and schedule that the patient previously received) beginning on day 1.

ARM B: Patients receive cetuximab as in Arm A and bevacizumab IV over 30-90 minutes on days 1*, 15, and 29.

NOTE: *Bevacizumab is given on day 2 (instead of day 1) of course 1, and is given on day 1 of subsequent courses.

In both arms, courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed for 3 years.

Being tested
cetuximab, bevacizumab, irinotecan hydrochloride, laboratory biomarker analysis
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms

What participants receive

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

  • cetuximabBiological

    Also called C225, C225 monoclonal antibody, IMC-C225, MOAB C225

    Given IV

  • bevacizumabBiological

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

    Given IV

  • irinotecan hydrochlorideDrug

    Also called Campto, Camptosar, CPT-11, irinotecan

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00077298
Study groupRoleWhat they receive
Arm A (cetuximab, bevacizumab, irinotecan)IExperimentalPatients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36; bevacizumab IV over 30-90 minutes on days 1*, 15, and 29 OR on days 1 and 22; and irinotecan IV over 30-90 minutes (at the same dose and schedule that the patient previously received) beginning on day 1. NOTE: *Bevacizumab is given on day 2 (instead of day 1) of course 1, and is given on day 1 of subsequent courses.
Receives: Biological: cetuximab; Biological: bevacizumab; Drug: irinotecan hydrochloride; Other: laboratory biomarker analysis
Arm B (cetuximab and bevacizumab)ExperimentalPatients receive cetuximab as in Arm A and bevacizumab IV over 30-90 minutes on days 1*, 15, and 29. NOTE: *Bevacizumab is given on day 2 (instead of day 1) of course 1, and is given on day 1 of subsequent courses.
Receives: Biological: cetuximab; Biological: bevacizumab; Other: laboratory biomarker analysis

What is being measured

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

  1. Time to tumor progression

    Measured: Date of randomization to the date of either documentation of disease progression, or death, assessed up to 3 years

Secondary outcomes (2)
  1. Objective response rate

    Measured: Up to 3 years

  2. Overall survival

    Survival probabilities will be computed using Kaplan-Meier methods and compared using the log-rank test.

    Measured: Up to 3 years

Timeline

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

  1. First posted11 Feb 2004 (estimated)
  2. Study startDec 2003
  3. Primary completionJul 2007
  4. Study completionJul 2007

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00077298
Sponsor's protocol ID
NCI-2012-01445
Other IDs
NCI-2012-01445, MSKCC-03135, NCI-6444, CDR0000350086, 03-135, 6444, N01CM17105, N01CM17101
Status last verified
Dec 2012
First submitted
10 Feb 2004
Last updated
15 Apr 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cetuximab, bevacizumab and irinotecan hydrochloride in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, run by National Cancer Institute (NCI) 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 69 inclusion and 0 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 15 Apr 2015. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Time to tumor progression (time frame: Date of randomization to the date of either documentation of disease progression, or death, assessed up to 3 years). 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 15 Apr 2015.

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