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Brain CancerPhase 2NCT01067469

Standard Dose Bevacizumab Versus Low Dose Bevacizumab Plus Lomustine (CCNU) for Recurrent Glioblastoma Multiforme (GBM)

A Phase 2 study testing Standard Dose Bevacizumab, Low Dose Bevacizumab and Lomustine in people with Brain Cancer and Glioblastoma, run by M.D. Anderson Cancer Center 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
Search all trials

Trial summary

The goal of this clinical research study is to learn if the combination of bevacizumab and lomustine can help to control glioblastoma. The safety of this combination will also be studied. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Brain Cancer, Glioblastoma
What is being tested?
Standard Dose Bevacizumab, Low Dose Bevacizumab and Lomustine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
83 participants
Where
1 siteUnited States
Study dates
Jan 2010to Oct 2016
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

  • Signed Informed Consent Form
  • Age >/= 18 years
  • Histologically confirmed glioblastoma in first, second or third relapse. A pathology report constitutes adequate documentation of histology for study inclusion. Subjects with an initial diagnosis of a lower grade glioma are eligible if a subsequent biopsy is determined to be glioblastoma. The amount of prior systemic therapy for this population is, nevertheless, restricted to three regimens, with one including temozolomide.
  • Radiographic demonstration of disease progression following prior therapy
  • Bi-dimensionally measurable disease with a minimum measurement of 1 cm (10 mm) in one diameter on MRI performed within 14 days prior to registration (Day 1). Baseline MRIs for subjects who underwent salvage surgery after first or second relapse must be obtained >/= 4 weeks after the procedure. If receiving corticosteroids, subjects must be on a stable or decreasing dose of corticosteroids for >/= 5 days prior to baseline MRI.
  • Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: 1) They have recovered from the effects of surgery. 2) Evaluable or measurable disease following resection of recurrent tumor is not mandated for eligibility into the study. 3) To best assess the extent of residual measurable disease post-operatively, a MRI should be done no later than 96 hours in the immediate post-operative period or 4-6 weeks post-operatively. .
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  • An interval of >/= 4 weeks since surgical resection is required prior to starting protocol therapy.
  • Prior standard radiation for glioblastoma
  • Prior chemotherapy: All first-relapse subjects must have received temozolomide. All second- and third-relapse subjects must have received temozolomide. Patients may not have received prior nitrosoureas.
  • Recovery from the effects of prior therapy, including the following: Four weeks from cytotoxic agents (3 weeks from procarbazine, 2 weeks from vincristine); Four weeks from any investigational agent; One week from non-cytotoxic agents(eg accutane, thalidomide); Eight weeks from radiotherapy to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field; Patients may have had gliadel wafers during their original surgery but they must be >/= 9 months post their original surgery date.
  • Prior therapy with gamma knife or other focal high-dose radiation is allowed, but the subject must have subsequent histologic documentation of recurrence or positron emission tomography (PET) or MR Spectroscopic documentation of tumor, unless the recurrence is a new lesion outside the irradiated field
  • Patients must have adequate bone marrow function (WBC >/= 3,000/µl, absolute neutrophil count (ANC) >/= 1,500/mm^3, platelet count of >/= 100,000/mm^3, and hemoglobin >/= 10 gm/dl), adequate liver function (SGPT < 3 times normal and alkaline phosphatase < 2 times normal, bilirubin <1.5 mg/dl), adequate renal function (creatinine </= 1.5 mg/dL or creatinine clearance >/= 60 cc/min/1.73 m^2) and a urine protein:creatinine ratio of </=1 before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
  • Patients must have a Karnofsky performance status (KPS) equal or greater than 60
  • Use of an effective means of contraception in males and in females of childbearing potential. Women of childbearing potential must have a negative β-human chorionic gonadotropin (HCG) pregnancy test documented within 14 days prior to registration. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to comply with study and follow-up procedures
  • Patients receiving treatment with other antiepileptic medications will not be excluded. Patients should preferably be treated with non-enzyme inducing anti-epileptic medications to avoid any potential interactions with lomustine. However, the use of non-enzyme inducing anti-epileptic medications is not mandatory. If enzyme-inducing antiepileptic drugs are used, monitoring of drug levels should be considered, as considered clinically appropriate by the treating physician.
  • Patients on the following medications will be included: Anticoagulants/Anti-platelets: Patients on stable dose anticoagulants (e.g. warfarin, low molecular-weight heparin) and in-range international normalized ratio (INR) (2-3) are eligible. Patients are allowed to take aspirin, clopidogrel, ticlopidine, Aggrenox, ibuprofen and other NSAIDS.
  • Patients must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while enrolled in the study.
  • This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. No exclusion to this study will be based on race. Minorities will actively be recruited to participate.

Who cannot join

  • Prior treatment with anti-angiogenesis (eg bevacizumab, sorafenib, sunitinib) agent or nitrosurea (eg. lomustine, carmustine, nimustine).
  • Prior treatment with polifeprosan 20 with carmustine wafer except for the patients with gliadel wafers >/= 9 months post their original surgery date.
  • Patients must not have received any investigational agents within 28 days prior to commencing study treatment.
  • Prior intracerebral agents
  • Need for urgent palliative intervention for primary disease (e.g., impending herniation)
  • Evidence of recent hemorrhage on baseline MRI of the brain with the following exceptions: (1) Presence of hemosiderin (2) Resolving hemorrhagic changes related to surgery (3) Presence of punctate hemorrhage in the tumor
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  • Blood pressure of > 140 mmHg systolic and > 90 mmHg diastolic
  • History of hypertensive encephalopathy
  • New York Heart Association (NYHA) Grade II or greater chronic heart failure(CHF)
  • History of myocardial infarction or unstable angina within 6 months prior to Day 1
  • History of stroke or transient ischemic attack within 6 months prior to study enrollment
  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 1
  • Evidence of bleeding diathesis or coagulopathy or INR >1.5 unless on a stable dose of anticoagulation therapy. History of significant bleeding disorder unrelated to cancer, including: (1) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) (2) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) (3) Ongoing or recent (</= 3 months) significant gastrointestinal bleeding
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
  • History of intracerebral abscess within 6 months prior to Day 1
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study
  • Minor surgical procedures (excluding placement of a vascular access device), stereotactic biopsy, fine needle aspirations, or core biopsies within 7 days prior to Day 1
  • Serious non-healing wound, ulcer, or bone fracture
  • Pregnancy (positive pregnancy test) or lactation
  • Known hypersensitivity to any component of bevacizumab
  • History of any other malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible
  • Pregnant or nursing females
  • Unstable systemic disease, including active infection, uncontrolled hypertension, or serious cardiac arrhythmia requiring medication
  • Subjects unable to undergo an MRI with contrast
  • Patients with a known allergy to bevacizumab, or a known allergy to nitrosoureas (eg. lomustine, carmustine, nimustine) will be excluded
  • Patient must be able to tolerate the procedures required in this study including periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study. Inability to comply with protocol or study procedures (for example, an inability to swallow tablets) will be an exclusion criteria.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Randomized Phase II Trial of Standard Dose Bevacizumab Versus Low Dose Bevacizumab Plus Lomustine (CCNU) In Adults With Recurrent Glioblastoma Multiforme

The goal of this clinical research study is to learn if the combination of bevacizumab and lomustine can help to control glioblastoma. The safety of this combination will also be studied.

Read the detailed description

The Study Drugs:

Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.

Lomustine is designed to damage the DNA (genetic material of cells) of tumor cells, which may cause the tumor cells to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups. You will have an equal chance of being in either group.

  • If you are in Group 1, you will receive a higher dose of bevacizumab.
  • If you are in Group 2, you will receive lomustine and a lower dose of bevacizumab

Study Drug Administration:

Each treatment cycle is 42 days.

If you are in Group 1:

On Days 1, 15, and 29 of every cycle, you will receive bevacizumab by vein over 90 minutes.

If you are in Group 2:

  • On Days 1 and 22 of every cycle, you will receive bevacizumab by vein over 90 minutes.
  • On Day 3 of every cycle, you will take lomustine by mouth 1 time a day. You should take lomustine at bedtime 1 hour before or 2 hours after your last meal of the day with 1 cup (about 8 ounces) of water.

Study Visits:

If you are in Group 1 or 2, every 6 weeks:

  • You will be asked about any drugs you may be taking and if you have had any side effects.
  • You will have a physical exam, including measurement of your vital signs and weight.
  • You will have a neurological exam.
  • Your performance status will be recorded.
  • You will have an MRI scan.
  • If you are on anti-seizure drugs, blood (about 1 teaspoon) will be drawn to measure the amount of anti-seizure drugs in your blood.

If you are in Group 1:

  • During Weeks 1-6, blood (about 3 teaspoons) drawn for routine tests 1 time a week.
  • After Week 6, blood (about 3 teaspoons) will be drawn for routine tests every 2 weeks.
  • On Weeks 2, 4, and 6, and then every 6 weeks after that, urine will be collected to check your kidney function.

If you are in Group 2:

  • During Weeks 1-6, blood (about 3 teaspoons) drawn for routine tests 1 time a week.
  • After Week 6, blood (about 3 teaspoons) will be drawn for routine tests every 3 weeks.
  • On Weeks 3 and 6, and then every 6 weeks after that, urine will be collected to check your kidney function.

Length of Study:

You may stay on study treatment of lomustine and/or bevacizumab for up to 1 1/2 years. After that, you may continue taking bevacizumab for as long as the study doctor thinks it is in your best interest. You will be taken off study early if the disease gets worse or you experience intolerable side effects.

End of Study Treatment Visit:

After you are off study treatment, you will have an end of study treatment visit. At this visit, you may have some or all of the following tests and procedures performed:

  • You will be asked about any drugs you may be taking and if you have had any side effects.
  • You will have physical exam, including measurement of your vital signs and weight.
  • Blood (about 3 teaspoons) will be drawn for routine tests.
  • You will have a neurological exam.
  • Your performance status will be recorded.

Long-Term Follow-up:

After the end of study treatment visit, the study staff will call you every 3 months to check how you are doing. Each phone call will take about 5 minutes.

This is an investigational study. Bevacizumab and lomustine are FDA approved drugs and commercially available for the treatment of brain tumors. The use of these drugs in this combination is investigational.

Up to 102 participants will take part in this study. All will be enrolled at MD Anderson.

Being tested
Standard Dose Bevacizumab, Low Dose Bevacizumab, Lomustine
Keywords
CNS, Central Nervous System, malignant brain tumor, Recurrent Glioblastoma Multiforme, GBM, Bevacizumab, Lomustine, CCNU
Medical subject headings
Brain Neoplasms, Glioblastoma

What participants receive

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

  • Standard Dose BevacizumabDrug

    Also called Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

    10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.

  • Low Dose BevacizumabDrug

    Also called Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

    5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle.

  • LomustineDrug

    Also called CeeNU, CCNU

    Starting dose of 75 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle.

Study groups in NCT01067469
Study groupRoleWhat they receive
Standard Dose BevacizumabExperimentalBevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.
Receives: Drug: Standard Dose Bevacizumab
Low Dose Bevacizumab + LomustineExperimentalBevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 75 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle.
Receives: Drug: Low Dose Bevacizumab; Drug: Lomustine

What is being measured

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

  1. Progression Free Survival (PFS)

    Participants with no disease progression as measured by magnetic resonance imaging (MRI) scans. Participants followed by MRI scans, as used for baseline tumor measurements, and removed from study if progression is documented after any cycle of treatment. PFS determined from date of registration in the trial and not date of randomization into chemotherapy arms (i.e. after surgery for resection of recurrent tumor).

    Measured: Documented from the date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year

Secondary outcomes (5)

  1. Radiographic Response (RR)

    Definition of Modified Radiographic Response Assessment Criteria for Glioblastoma (GBM) . Complete, Partial, Progressive Disease and Stable Disease. Radiographic response determined in comparison to the tumor measurements obtained at baseline (post-radiation scan will be baseline for newly diagnosed GBM and pre-treatment scans will be the baseline for recurrent GBM) for determination of response, and the smallest tumor measurement at either pre-treatment baseline or following initiation of therapy for determining progression.

    Measured: One year

  2. 6-month Progression-free Survival (PFS-6)

    Participants with no disease progression as measured by magnetic resonance imaging (MRI) scans. Participants followed by MRI scans, as used for baseline tumor measurements, and removed from study if progression is documented after any cycle of treatment. PFS determined from date of registration in the trial and not date of randomization into chemotherapy arms (i.e. after surgery for resection of recurrent tumor).

    Measured: 6 Months

  3. Overall Survival (OS)

    Overall Survival(OS) is defined: Time of presentation to date of death or censored at last follow-up date

    Measured: through study completion, an average of 2 years

  4. Time to Progression (TTP)

    TTP is defined as the time from randomization to time of progressive disease

    Measured: Up to One year

  5. Summary of Treatment Related Toxicities

    Adverse Events grade 3 and 4 hematologic toxicities reported in safety profile of bevacizumab (Avastin) in combination with Lomustine in patients with recurrent glioblastoma using Common Terminology Criteria for Adverse Events (CTCAE) version 3.

    Measured: One year

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 2010 (estimated)
  2. Study startJan 2010
  3. Primary completionOct 2016
  4. Study completionOct 2016

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
Single group
Masking
None (open label)
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01067469
Sponsor's protocol ID
2009-0597
Other IDs
NCI-2011-00559
Status last verified
Mar 2020
First submitted
10 Feb 2010
Last updated
17 Mar 2020
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Standard Dose Bevacizumab, Low Dose Bevacizumab and Lomustine in people with Brain Cancer and Glioblastoma, run by M.D. Anderson Cancer Center 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 19 inclusion and 26 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 Mar 2020. 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?

Yes. Results are posted in the registry (first posted 17 Mar 2020). 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?

Progression Free Survival (PFS) (time frame: Documented from the date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 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 NCT01067469.

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 Mar 2020.

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