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Recurrent Breast CarcinomaPhase 2NCT00054132

Erlotinib Hydrochloride and Bevacizumab in Treating Patients With Stage IV Breast Cancer

A Phase 2 study testing Bevacizumab, Erlotinib Hydrochloride and Laboratory Biomarker Analysis in people with Recurrent Breast Carcinoma and Stage IV Breast 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 II trial studies how well erlotinib hydrochloride and bevacizumab work in treating patients with stage IV breast cancer. Erlotinib hydrochloride 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, women only
What is being tested?
Bevacizumab, Erlotinib Hydrochloride and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
2 sitesUnited States
Study dates
Dec 2002to Apr 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically or cytologically confirmed carcinoma of the breast with metastatic (stage IV) disease that is currently stable or progressing after therapy
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan
  • Patients must have either stable disease or disease progression on or after therapy with one or two conventional chemotherapy regimens for the treatment of metastatic (stage IV) breast cancer
  • Prior treatment with high-dose chemotherapy and autologous stem cell/bone marrow transplantation is allowed, and is considered one prior regimen when administered for metastatic disease
  • There is no restriction for the number of prior hormonal therapies or immunotherapies
  • If human epidermal growth factor receptor 2 (Her2)/neu-positive (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescence in situ hybridization [FISH]), prior therapy with trastuzumab required
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  • Any number of prior regimens of chemotherapy and/or hormonal therapy are allowed in the adjuvant setting, and do not count towards prior therapy when determining eligibility for this trial
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3,000/ul
  • Absolute neutrophil count >= 1,000/ul
  • Platelets >= 75,000/ul
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT[) =< 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min for patients with creatinine levels outside institutional normal using the Cockcroft-Gault formula
  • Women of childbearing potential must agree to use adequate contraception (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
  • Patients must have breast cancer tissue available as either paraffin blocks or unstained slides for planned correlative science sub study
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients who have had chemotherapy, radiotherapy immunotherapy or investigational therapy within 3 weeks prior to starting treatment (6 weeks for nitrosoureas or mitomycin C), or hormonal therapy within 2 weeks prior to starting treatment
  • Patients may not be receiving any other investigational agents
  • History or evidence upon physical examination of central nervous system (CNS) disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of stroke); all subjects must have a baseline CT or magnetic resonance imaging (MRI) of the head
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to OSI-774 or bevacizumab
  • Prior treatment with kinase insert domain receptor (KDR) inhibitors (e.g. vascular endothelial growth factor [VEGF] Trap, Su5416, Su6668, ZD6474, PTK757, IMC-1CII)
  • Prior treatment with EGFR targeting therapies (e.g. ZD1839 or C225)
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  • Major surgery, open biopsy or significant traumatic injury occurring within 28 days prior to treatment; this does not apply to indwelling catheters, which require an interval of at least 24 hours between placement of the catheter and treatment with bevacizumab
  • Current or recent (within 10 days prior to treatment) 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] should be < 1.5)
  • Chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit the platelet function (e.g. cyclooxygenase [COX]-1 inhibitors)
  • Presence of bleeding diathesis or coagulopathy
  • Cumulative anthracycline and anthracenedione exposure as follows: doxorubicin > 450 mg/m^2; epirubicin > 700 mg/m^2; liposomal doxorubicin > 550 mg/m^2; mitoxantrone > 140 mg/m^2
  • Proteinuria at baseline; subjects unexpectedly discovered to have >= 1+ proteinuria should undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate =< 500 mg protein/ 24 hours to allow participation in the study
  • Cardiac ejection fraction (multigated acquisition scan [MUGA] or echocardiogram) less than the local institution lower limit of normal
  • Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjögren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)
  • Serious, non-healing wound, ulcer, or bone fracture
  • Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, myocardial infarction, unstable angina), 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
  • Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, or prior surgical procedures affecting absorption
  • 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; breastfeeding should be discontinued if the mother is treated with OSI-774
  • Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study
  • Patients with recent (within 6 months) arterial thrombotic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, myocardial infarction (MI), or clinically significant peripheral artery disease

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • UCSF Medical Center-Mount Zion

    San Francisco, California, 94115

Other trials in United States

About this study

Official title: A Phase II Study of OSI-774 in Combination With Bevacizumab in Patients With Stage IV Breast Cancer

This phase II trial studies how well erlotinib hydrochloride and bevacizumab work in treating patients with stage IV breast cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Giving erlotinib hydrochloride and bevacizumab may be an effective treatment for breast cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the efficacy of bevacizumab in combination with OSI-774 (erlotinib hydrochloride) in patients with previously treated metastatic breast cancer, as measured by objective response rate.

SECONDARY OBJECTIVES:

  1. To determine the toxicity of bevacizumab in combination with OSI-774 in patients with previously treated metastatic breast cancer.

II. To evaluate the efficacy of bevacizumab in combination with OSI-774 in patients with previously treated metastatic breast cancer, as measured by time to disease progression, duration of response and the proportion of patients with stabilization of disease >= 6 months.

III. To determine the molecular profile of the patient's primary breast tumor, and to explore the relationship between these molecular characteristics and the response to treatment.

IV. To explore changes in biological markers in pre- and post-treatment tumor tissue in a subset of patients with accessible sites of disease.

  1. To explore a pre- and post-treatment analysis of circulating endothelial cells and the relationship of this analysis to serum markers of angiogenesis as well as response to treatment.

VI. To obtain serial measurements of circulating epithelial cells and explore the relationship of these cells with circulating endothelial cells, markers of angiogenesis, and epidermal growth factor receptor (EGFR) expression.

OUTLINE:

Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21 and bevacizumab intravenously (IV) over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Being tested
Bevacizumab, Erlotinib Hydrochloride, Laboratory Biomarker Analysis
Medical subject headings
Breast 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, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • Erlotinib HydrochlorideDrug

    Also called Cp-358,774, OSI-774, Tarceva

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT00054132
Study groupRoleWhat they receive
Treatment (erlotinib hydrochloride, bevacizumab)ExperimentalPatients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Bevacizumab; Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Level of EGFR Expression

    Estimated at the end of the trial Immunoreactivity will be evaluated qualitatively with regard to intensity as follows: Measured on a scale, ranging from 0-3+ 0=negative (no immunoreactivity)

    1+ - 3+ = positive:

    • faint immunoreactivity (weak staining)
    • intense immunoreactivity (strong staining) Immunohistochemical studies will be performed on the tumor specimen to correlate the anti-tumor efficacy of OSI-774 and bevacizumab with pre-treatment molecular characteristics.

    Measured: Up to 12 years

  2. Response Rate, Defined as Complete Response (CR) + Partial Response (PR), Using the Response Evaluation Criteria in Solid Tumors

    Estimated at the end of the trial. Complete Response (CR):Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD 55 Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

    Measured: Up to 12 years

Secondary outcomes (4)

  1. Duration of Response

    The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).Evaluation of Target Lesions Complete Response (CR):Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD

    Measured: From the time measurement criteria are met for CR and PR until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 years

  2. Time to Progression

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Measured: From the start of treatment until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 years

  3. Number of Patients Evaluated for Toxicity

    graded according to the National Cancer Institute Common Toxicity Criteria version 4.0

    Measured: up to 12 years

  4. Participants With Duration of Stable Disease Greater Than or Equal to 6 Months

    Duration of stable disease greater than or equal to 6 months

    Measured: From the start of treatment until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 years

Timeline

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

  1. First posted6 Feb 2003 (estimated)
  2. Study startDec 2002
  3. Primary completionApr 2015
  4. Study completionApr 2015

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00054132
Sponsor's protocol ID
NCI-2013-02225
Other IDs
NCI-2013-02225, CDR0000269900, 02-119, MSKCC-02119, NCI-5761, 02-119, 5761, N01CM17105
Status last verified
Jun 2017
First submitted
5 Feb 2003
Last updated
24 Jul 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab, Erlotinib Hydrochloride and Laboratory Biomarker Analysis in people with Recurrent Breast Carcinoma and Stage IV Breast 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 18 inclusion and 21 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 24 Jul 2017. 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 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?

Yes. Results are posted in the registry (first posted 24 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Level of EGFR Expression (time frame: Up to 12 years). 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 NCT00054132.

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 24 Jul 2017.

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