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Brain CancerPhase 1NCT01392209

Hypofractionated Stereotactic Radiotherapy With Bevacizumab in the Treatment of Recurrent Malignant Glioma

A Phase 1 study testing Bevacizumab & Stereotactic Radiotherapy in people with Brain Cancer and MALIGNANT GLIOMA, run by Memorial Sloan Kettering Cancer Center at 5 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

The best dose of radiation to be given with bevacizumab is currently unknown. This study will use higher doses of radiation with bevacizumab than have been used before. This study will test the safety of radiation given at different doses with bevacizumab to find out what effects, good and/or bad, it has on the… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Brain Cancer, MALIGNANT GLIOMA, Glioblastoma
What is being tested?
Bevacizumab & Stereotactic Radiotherapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
5 sitesUnited States
Study dates
8 Jul 2011to 15 Nov 2019
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

  • Patients must have EITHER
  • Histologically confirmed intracranial malignant glioma of the following types: Glioblastoma, Anaplastic astrocytoma (AA), Anaplastic oligodendroglioma (AO), Anaplastic oligo-astrocytoma (AOA) also called anaplastic mixed gliomas, Malignant glioma NOS (not otherwise specified). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a high grade (malignant) glioma is made.
  • OR
  • Histologically confirmed low grade (WHO grade II) gliomas (such as low grade astrocytoma, low grade oligodendroglioma, low grade oligo-astrocytoma (mixed gliomas), or low grade glioma NOS) IF there is radiographic evidence by MRI of malignant transformation but histologic confirmation of high grade (malignant) transformation would not be otherwise undertaken for routine clinical care. Inclusion of patients in this group will allow increased accrual rapidity by enrolling patients who are otherwise ineligible for almost all malignant glioma trials yet whom are treated presumptively for malignant glioma. The primary aim of the phase I study is not determination of efficacy. Therefore, inclusion of such patients will not affect efficacy analyses.
  • Participating site confirmation is adequate.
  • Able to undergo brain MRI scans.
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  • MRI scan with gadolinium contrast showing geographically-circumscribed tumor ≤40 cc incorporating both enhancing and non-enhancing volume. This is calculated by the product of maximum measurements in 3 dimensions divided by 2. Tumors exceeding this limit may be eligible and any question should be directed to a Radiation Oncology Investigator and the MSK PI. (The MRI must be performed on a steroid dosage that has been stable or decreasing for at least 5 days. Patients on no steroids are eligible. If the steroid dose is increased between date of imaging and registration, a new baseline MRI is required).
  • Prior treatment with approximately 60 Gy of radiotherapy.
  • Patients must have recovered from the toxic effects of prior therapy including but not limited to:
  • An interval of ≥ 4 weeks (28 days) from prior cytotoxic therapy except 6 weeks from nitrosoureas
  • An interval of ≥ 1 week (7 days) from any non-cytotoxic agents
  • An interval of ≥ 3 months from the completion of radiation therapy
  • Absolute neutrophil count ≥ 1,500/mm3.
  • Platelet count ≥ 100,000/mm3.
  • Hemoglobin ≥ 10 g/dl.
  • Serum creatinine ≤ 2 times upper limit of normal.
  • Total bilirubin ≤ 2 times upper limit of normal.
  • SGOT and SGPT both ≤ 3 times upper limit of normal.
  • ≥18 years of age.
  • Karnofsky Performance Score ≥ 60
  • Life expectancy ≥ 12 weeks
  • Men and women with reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
  • Written informed consent prior to registration on study.

Who cannot join

  • Prior treatment with radiosurgery
  • Prior disease progression/recurrence during or immediately following treatment with bevacizumab. Any question should be directed to the PI.
  • Multicentric glioma
  • Other malignancy (with the exception of cervical carcinoma in situ or basal cell carcinoma of the skin) for which there has been treatment within the last 3 years
  • Serious medical or psychiatric illness that would in the opinion of the investigator interferes with the prescribed treatment.
  • Pregnant or breast feeding women
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  • Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg)
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • Grade 2 or greater congestive heart failure
  • History of myocardial infarction, unstable angina, stroke, or transient ischemic attack within 12 months prior to Day 1
  • Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
  • History of hemoptysis ≥1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of treatment or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
  • Serious, non-healing wound, active ulcer, or untreated bone fracture
  • Proteinuria as demonstrated by a UPC ratio ≥ 1.0 at screening
  • Known hypersensitivity to any component of bevacizumab
  • History of peptic ulcer within the last 6 months
  • Clinically significant peripheral vascular disease
  • Craniotomy wound that has not sufficiently healed
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
  • Glioma showing prior spontaneous hemorrhage as determined from the clinical history or from any preoperative CT or MRI scan (excluding grade 1 punctate, incidentally found).
  • Longest uni-dimensional measurement of contrast enhancing tumor ≥ 4cm. Tumors exceeding this limit may be eligible and any question should be directed to a Radiation Oncology Investigator and the MSK PI.
  • Tumor must not invade the corpus callosum
  • Tumor must not invade the brainstem
  • Suspected or documented radionecrosis

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of California San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: A PHASE I DOSE ESCALATION STUDY OF HYPOFRACTIONATED STEREOTACTIC RADIOTHERAPY WITH BEVACIZUMAB IN THE TREATMENT OF RECURRENT MALIGNANT GLIOMA

The best dose of radiation to be given with bevacizumab is currently unknown. This study will use higher doses of radiation with bevacizumab than have been used before. This study will test the safety of radiation given at different doses with bevacizumab to find out what effects, good and/or bad, it has on the patient and the malignant glioma or related brain cancers.

Being tested
Bevacizumab & Stereotactic Radiotherapy
Keywords
BEVACIZUMAB, HYPOFRACTIONATED STEREOTACTIC RADIOTHERAPY, Brain, CNS, anti-VEGF antibody, 11-057
Medical subject headings
Brain Neoplasms, Glioma, Glioblastoma, Astrocytoma, Oligodendroglioma

What participants receive

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

  • Bevacizumab & Stereotactic RadiotherapyOther

    Treatment: (until treatment failure): bevacizumab 10 mg/kg IV once every two weeks on days 1 (+/- 3 days) and 15 (+/- 3 days) of every cycle (Cycle defined as 28 days). On day 28 (or up to 2 days before) of cycles 1 and 2 (and for every other cycle thereafter) patients will undergo a physical and radiological re-evaluation (MRI). Patients will begin stereotactic radiotherapy beginning anywhere from day 7 to day 10 of cycle 2 with escalating fraction sizes (interpatient - there is no intrapatient escalation). Assessment of response will be performed following cycles 1 and 2 then following every two cycles.

Study groups in NCT01392209
Study groupRoleWhat they receive
Bevacizumab & Stereotactic RadiotherapyExperimentalThis will be a multicenter (MSKCC and UCSF) phase I dose escalation study to determine the maximum tolerated dose (MTD) of hypofractionated stereotactic radiotherapy when administered in combination with a fixed dose of bevacizumab.
Receives: Other: Bevacizumab & Stereotactic Radiotherapy

What is being measured

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

  1. To establish the maximum tolerated dose (MTD)

    of hypofractionated stereotactic re-irradiation delivered with concomitant bevacizumab in recurrent malignant gliomas (using a standard 3+3 design).

    Measured: 1 year

Secondary outcomes (6)

  1. Response rate

    Median overall survival and progression-free survival, along with the estimated survival and PFS rates at specified time points will be estimated using Kaplan-Meier method. Confidence intervals will be included with all point estimates. Response rate will be estimated using an exact binomial distribution together with 95% confidence interval.

    Measured: 1 year

  2. Median progression free survival

    Median overall survival and progression-free survival, along with the estimated survival and PFS rates at specified time points will be estimated using Kaplan-Meier method. Confidence intervals will be included with all point estimates. Response rate will be estimated using an exact binomial distribution together with 95% confidence interval.

    Measured: 1 year

  3. 6 month progression-free survival rate

    Median overall survival and progression-free survival, along with the estimated survival and PFS rates at specified time points will be estimated using Kaplan-Meier method. Confidence intervals will be included with all point estimates. Response rate will be estimated using an exact binomial distribution together with 95% confidence interval.

    Measured: 1 year

  4. Median overall survival

    Median overall survival and progression-free survival, along with the estimated survival and PFS rates at specified time points will be estimated using Kaplan-Meier method. Confidence intervals will be included with all point estimates. Response rate will be estimated using an exact binomial distribution together with 95% confidence interval.

    Measured: 1 year

  5. Use of tractography to predict routes of progression in gliomas (MSKCC only)

    DTI will be acquired at the time of the patient's routinely scheduled brain MRIs but at least on the baseline scan and the MRI 1 month after cycle 2. DTI parameters: A spin-echo echo-planar sequence using 25 gradient directions, TR/TE 11000/100 msec; matrix 128 × 128; in-plane resolution 1.88 × 1.88 mm; slice thickness 3 mm; b-value 1000 sec/mm2; NEX 1 and maximum diffusion gradient strength 22mTm-1.

    Measured: 1 year

  6. Correlation of VEGF and VEGFR IHC and related pathways (MSKCC only) and MGMT promoter methylation with efficacy

    Exploratory analyses related to VEGFR signaling including IHC for VEGF and VEGFR on pre-treatment tissue and post-treatment tissue and the analysis of biological correlate data has the overall goal of providing increased understanding of the nature of the response to bevacizumab but the amount of data available for the various measures is uncertain. Information may also be limited by the impact of intervening treatment between the most recent surgery and initiation of study treatment.

    Measured: 1 year

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 2011 (estimated)
  2. Study start8 Jul 2011
  3. Primary completion15 Nov 2019
  4. Study completion15 Nov 2019

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
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01392209
Sponsor's protocol ID
11-057
Status last verified
Nov 2019
First submitted
8 Jul 2011
Last updated
22 Nov 2019
Results posted
No

Publications

  • Clarke J, Neil E, Terziev R, Gutin P, Barani I, Kaley T, Lassman AB, Chan TA, Yamada J, DeAngelis L, Ballangrud A, Young R, Panageas KS, Beal K, Omuro A. Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma. Int J Radiat Oncol Biol Phys. 2017 Nov 15;99(4):797-804. doi: 10.1016/j.ijrobp.2017.06.2466. Epub 2017 Jun 30.

    PubMed 28870792

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bevacizumab & Stereotactic Radiotherapy in people with Brain Cancer and MALIGNANT GLIOMA, run by Memorial Sloan Kettering Cancer Center at 5 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 23 inclusion and 27 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 22 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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?

To establish the maximum tolerated dose (MTD) (time frame: 1 year). 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 NCT01392209, which also lists 1 linked publication.

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 22 Nov 2019; AzTrials last refreshed its copy on 8 Nov 2026.

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