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Metastatic CancerPhase 2NCT01898130

Bevacizumab in Pats w/ Recurrent ST Brain Metas Who Have Failed Whole Brain Radiation Therapy

A Phase 2 study testing bevacizumab and quality-of-life assessment in people with Metastatic Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by Northwestern University at 4 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

This is a study to evaluate a drug called bevacizumab in patients with cancer whose disease has spread to their brain. This study will not evaluate the effect of bevacizumab on the systemic solid tumor cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
bevacizumab and quality-of-life assessment
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
4 sitesUnited States
Study dates
27 Nov 2013to 5 Sep 2018
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have a histologically or cytologically confirmed non-central nervous system (CNS) primary solid malignancy at the time of initial diagnosis; NOTE: brain lesions are not required to have pathologic confirmation; in addition, a copy of the pathology report for the primary tumor is sufficient for registration purposes
  • Patients must have radiographically-confirmed recurrent brain metastases from a solid tumor after WBRT
  • Patients must have measurable or evaluable disease in the brain
  • Patients must have been on a stable dose of corticosteroids >= 5 days prior to obtaining their baseline gadolinium (Gd)-MRI of brain
  • Patients must have completed WBRT > 12 weeks prior to enrollment to limit cases of pseudoprogression; however if new lesions are noted < 12 weeks but > 4 weeks prior to enrollment, those patients are eligible
  • Patients who underwent radiosurgery to treat a progressive lesion must have confirmation of tumor by tissue, magnetic resonance spectroscopy (MRS), magnetic resonance (MR) perfusion or positron emission tomography (PET) and the lesion must be measurable; NOTE: radiosurgery may be done to a lesion that will not be used for response evaluation and should be done > 2 weeks prior to enrollment
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  • Patients may be on other systemic chemotherapies if progressive CNS disease occurs while on these treatments; NOTE: new systemic chemotherapies should not be started unless required to treat systemic disease and should not start until at least 1 follow up imaging study has been performed
  • Patients may have received any number of prior CNS directed therapies - there are no limitations
  • Patients must have a life expectancy of >= 12 weeks
  • Patients must have a Karnofsky performance score (KPS) of >= 60
  • Whole blood cell (WBC) >= 3,000/ul
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Hemoglobin >= 10 gm/dl (may be reached by transfusion)
  • Serum glutamic oxaloacetic transaminase (SGOT) < 2 x upper limit of normal (ULN) (or < 5 x ULN if liver is involved)
  • Bilirubin < 2 x ULN (or < 5 x ULN if liver is involved)
  • Creatinine < 1.5 x ULN
  • Patients of both sexes must agree to the use of barrier contraceptives throughout the duration of treatment on this trial and for 3 months after discontinuing treatment; NOTE: hormonal contraceptives are not acceptable as a sole method of contraception
  • Patients must be > 4 weeks from any major surgery
  • Patients NOT on warfarin must have a prothrombin time (PT)/international normalized ratio (INR) < 1.4 within 14 days prior to registration
  • Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight [LMW] heparin) must meet BOTH of the following criteria within 14 days prior to registration:
  • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  • In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of LMW heparin
  • Female patients of child-bearing potential must have a negative pregnancy test within 14 days prior to registration
  • Patients must be willing and able to comply with study and/or follow-up procedures
  • Patients must sign an informed consent prior to registration and before undergoing any study-specific procedures indicating that they are aware of the investigational nature of this study

Who cannot join

  • Patients with a diagnosis of intrathoracic lung carcinoma of squamous cell histology are not eligible for participation
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using barrier birth control methods, are not eligible for participation
  • Patients must not have baseline proteinuria within 14 days prior to registration as demonstrated by either:
  • Urine protein: creatinine (UPC) ratio < 1.0 at screening, OR
  • Urine dipstick for proteinuria =< 2+; NOTE: patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1g of protein in 24 hours to be eligible
  • Patients must not have experienced any major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, or be anticipated to need a major surgical procedure during the course of the study; NOTE: the exception is craniotomy
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  • Patients must not have experienced a core biopsy or other minor surgical procedure within 7 days prior to registration; NOTE: this excludes placement of a vascular access device
  • Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the previous 6 months are not eligible for participation
  • Patients with a serious, non-healing wound, ulcer, or bone fracture are not eligible for participation due to the effects on vasculature by bevacizumab which may impair healing
  • Patients known to be human immunodeficiency virus (HIV) or hepatitis B and/or C positive are not eligible for participation; NOTE: HIV and hepatitis testing is not required for study participation
  • Patients with a history of any other cancer (except for non-melanoma skin cancer or carcinoma in-situ of the cervix), are not eligible for participation unless they are in complete remission and have been off of all therapy for that disease for a minimum of 3 years
  • Patients receiving or participating on any other experimental agents/clinical trials are not eligible for participation
  • Patients with a known hypersensitivity to any component of bevacizumab are not eligible for participation
  • Patients with any significant medical illnesses or infection that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy are not eligible for participation
  • Patients with leptomeningeal disease are not eligible for participation
  • Patients who have received previous treatment with bevacizumab for CNS disease are not eligible for participation
  • Patients with inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg) are not eligible for participation

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • Northwestern Memorial Hospital: Lake Forest Hospital

    Lake Forest, Illinois, 60045

  • Columbia University Medical Center

    New York, New York, 10032

  • Cadence Health - CDH

    Warrenville, Illinois, 60555

Other trials in United States

About this study

Official title: A Phase II Trial of Bevacizumab in Patients With Recurrent Solid Tumor Brain Metastases Who Have Failed Whole Brain Radiation Therapy

This is a study to evaluate a drug called bevacizumab in patients with cancer whose disease has spread to their brain. This study will not evaluate the effect of bevacizumab on the systemic solid tumor cancer. Bevacizumab is a medication and it is thought that bevacizumab may interfere with the growth of new blood vessels; therefore it might stop tumor growth and possibly shrink the tumor by keeping it from receiving nutrients and oxygen supplied by the blood vessels.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the radiographic response rate in patients with solid tumor brain metastases treated with bevacizumab.

SECONDARY OBJECTIVES:

  1. Estimate the progression-free survival (PFS) rate at 6 months. II. Determine the time to progression based on magnetic resonance imaging (MRI) or computed tomography (CT) scans.

III. Determine the time to response based on radiographic imaging. IV. Determine the duration of response based on radiographic imaging. V. Determine overall survival. VI. Collect additional safety data. VII. Assess changes in quality of life using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) while on treatment.

OUTLINE:

Patients receive bevacizumab intravenously (IV) over 30-90 minutes every 2 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8 weeks.

Being tested
bevacizumab, quality-of-life assessment
Medical subject headings
Neoplasm Metastasis

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

  • quality-of-life assessmentProcedure or surgery

    Also called quality of life assessment

    Ancillary studies

Study groups in NCT01898130
Study groupRoleWhat they receive
Treatment (bevacizumab)ExperimentalPatients receive bevacizumab IV over 30-90 minutes every 2 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: bevacizumab; Procedure: quality-of-life assessment

What is being measured

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

  1. Objective Radiographic Tumor Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab

    Radiographic Response to treatment will be assessed prior to every odd-numbered cycle using CT or MRI scans until disease progression, unacceptable toxicity as assessed by the Response Assessment in Neuro-Oncology (RANO) Criteria for target lesions. Response is defined as the number of patients with Complete Response (CR) plus those with Partial Response (PR) radiographically. Generally CR is defined as the disappearance of all target lesions and PR is defined as >=50% decrease in the sum of the longest diameter of target lesions.

    Measured: Every other cycle, starting cycle 3 (1 cycle =28 days) until off study. Range of cycles completed 1-20.

Secondary outcomes (7)

  1. Progression-Free Survival (PFS) at 6 Months in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab

    Progression-Free Survival (PFS) will be measured as the time from the first dose to the first occurrence of progression or death for any reason. To estimate PFS, Kaplan-Meier curves will be calculated and PFS at 6 months will be determined from the progression-free survival curve.

    Progression is defined using Response Assessment in Neuro-Oncology Criteria (RANO), as a 25% or more 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: At 6 months from treatment initiation.

  2. Time to Progression in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab

    MRI or CT scans and clinical assessment will be used to measure Time to Progression which will be assessed as the time from the date of first dose to the date of first observation of progressive disease, non-reversible neurologic progression or increasing steroid requirements, or early discontinuation of treatment as assessed by the RANO Criteria in those patients that experience response.

    Measured: From treatment initiation, every 2 cycles (1 cycle = 28 days) until progressive disease. Range of cycles completed 1-20.

  3. Time to Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab

    MRI or CT scans and clinical assessment will be used to measure Time to Response which will be assessed as the time from the date of first dose to the date of first observed tumor response in all patients that a response is observed. Response to treatment will be assessed using the Response Assessment in Neuro-Oncology (RANO) Criteria for target lesions. Response is defined as either Complete Response (CR) or a Partial Response (PR) radiographically. Generally CR is defined as the disappearance of all target lesions and PR is defined as >=50% decrease in the sum of the longest diameter of target lesions.

    Measured: From the start of treatment every 2 cycles (1 cycle =28 days) until time of response. Range of cycles completed 1-20.

  4. Duration of Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab

    The Duration of Overall Response is measured from the time measurement criteria are met for Complete Response (CR) or Partial Response (PR) until the first date that recurrent or Progressive Disease (PD) is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Duration of response will be based on CT or MRI scans and clinical assessment performed prior to every odd-numbered cycle to detect date of first response to study treatment until date of disease progression and assessed by the Response Assessment in Neuro-Oncology (RANO) Criteria for target lesions. Generally CR is defined as the disappearance of all target lesions, PR is defined as >=50% decrease in the sum of the longest diameter of target lesions and PD is defined as a 25% or more 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 documentation of response, every two cycles (1 cycle =28 days) until progressive disease. Range of cycles completed 1-20.

  5. Overall Survival (OS) in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab

    Overall Survival (OS) will be measured as the date of first dose of bevacizumab to the date of death from any cause. To estimate OS, Kaplan-Meier curves will be calculated and OS will be determined from the overall survival curve.

    Measured: From start of treatment until death from any cause. Median follow up of 8 months (range 1.3 to 47.9 months)

  6. Toxicity of Bevacizumab in Patients With Recurrent Solid Tumor Brain Metastases

    Adverse events (AE) will be collected at the start of every cycle and graded according NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. All AEs that are determined to be grade 3 or higher and at least possible related to bevacizumab will be reported for toxicity. In general AEs will be graded:

    Grade 1 - Mild: the event causes discomfort without disruption of normal daily activities.

    Grade 2 - Moderate: the event causes discomfort that affects normal daily activities.

    Grade 3 - Severe: the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status.

    Grade 4 - Life-threatening: the patient was at risk of death at the time of the event.

    Grade 5 - Fatal: the event caused death.

    Measured: Assessed prior to every cylcle (cycle=28 days) while on treatment through 30 days post last dose. Range of cycles 1-20.

  7. Quality of Life Assessments in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab

    Changes in quality of life will be evaluated using questionnaires (FACT-Br) at baseline (before treatment initiation) and at cycle 3.

    Four FACT scales were calculated. The higher the value the better the score, i.e., the better the quality of life perceived by patient.

    FACT-G (Fact General, possible range 0 - 108) BrCS (Brain Cancer Subscale, possible range 0 - 92) TOTAL (FACT-G + BrCS, possible range 0 - 200) TOI (Trial Outcome Index = Physical Well Being _ Functional Well Being +BrCS, possible range 0 - 148)

    Measured: Baseline and at Cycle 3 (1 Cycle = 28 days).

Timeline

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

  1. First posted12 Jul 2013 (estimated)
  2. Study start27 Nov 2013
  3. Primary completion23 Mar 2017
  4. Study completion5 Sep 2018

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
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01898130
Sponsor's protocol ID
NU 12C06
Other IDs
NCI-2013-00448, STU00080404
Status last verified
Mar 2019
First submitted
28 Jun 2013
Last updated
17 Sep 2019
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bevacizumab and quality-of-life assessment in people with Metastatic Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by Northwestern University at 4 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 26 inclusion and 17 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 17 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 25 Apr 2019). 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?

Objective Radiographic Tumor Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab (time frame: Every other cycle, starting cycle 3 (1 cycle =28 days) until off study. Range of cycles completed 1-20.). 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 NCT01898130.

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 17 Sep 2019.

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