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Brain CancerPhase 2NCT00883688

Bevacizumab and Lapatinib in Children With Recurrent or Refractory Ependymoma

A Phase 2 study testing Bevacizumab and Lapatinib in people with Brain Cancer and Pediatric Cancers, run by M.D. Anderson Cancer Center at 6 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

The goal of this clinical research study is to learn if the combination of Avastin (bevacizumab) and Tykerb (lapatinib) can help to control ependymoma in pediatric patients. The safety of this drug combination will also be studied. Read more about this study

Who is it for?
Ages Up to 21 years
Conditions the study is for
Brain Cancer, Pediatric Cancers
What is being tested?
Bevacizumab and Lapatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
6 sitesUnited States
Study dates
Jul 2009to 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 Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age: Patient must be < or = 21 years of age.
  • Tumor: Patients must have recurrent or refractory intracranial ependymoma (including myxopapillary, clear cell, papillary, tanycytic, and anaplastic ependymoma) or subependymoma. Patients with primary diagnosis of intracranial ependymoma with spinal cord metastases or relapse are eligible. The diagnosis must be confirmed by the CERN enrolling site's pathologist on tissue from either the initial presentation or time of recurrence prior to registration. For central pathology review and trial biological studies, submission of a paraffin block with tumor measuring at least 1 cm x 1 cm in area is preferred, but 15 x 5micro m unstained sections on slides may be provided by the referring laboratory instead. Tissue must be submitted within 60 days after enrollment for central processing and analysis.
  • Patients must have measureable disease which is defined as at least one measurable lesion that can be accurately measured in 2 planes. Diffuse leptomeningeal involvement ("sugar coating") that does not allow measurement of at least one lesion in 2 planes will not be considered measurable disease.
  • Patients may have had any number of prior treatment regimens (including biologic) before or after radiotherapy. Patients may not have previously been treated with Bevacizumab or Lapatinib. Gliadel wafers must be approved by CERN PI (Project Leader, Co-Leader and Protocol PI).
  • Neurological Deficits: Patients with neurological deficits should have deficits that are stable or improving for a minimum of 1 week prior to registration.
  • Performance Score: Karnofsky Performance Scale (KPS for > 16 years of age) or Lansky Performance Score (LPS for < or = 16 years of age) > or = 50 assessed within 2 weeks prior to registration.
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  • Evidence of recovery from any prior chemotherapy. No myelosuppressive anticancer chemotherapy or biological therapy within 3 weeks (6 weeks if a nitrosourea or mitomycin C agent) prior to registration.
  • Prior/Concurrent Therapy: external beam radiation therapy (XRT): Patients must have had prior radiation therapy for treatment of their ependymoma. XRT must be > or = 3 months prior to registration for craniospinal irradiation (> or = 18 Gy); > or = 4 weeks for local radiation to primary tumor; and > or = 2 weeks prior to registration for focal irradiation to symptomatic metastatic sites.
  • Prior/Concurrent Therapy: Bone Marrow Transplant: > or = 3 months prior to registration for autologous bone marrow/stem cell transplant.
  • Prior/Concurrent Therapy: Anti-convulsants: Patients with seizure disorder may be enrolled if well controlled. Patients receiving enzyme-inducing anticonvulsants are not eligible for this study. Patients must be off EIACD for at least 2 weeks prior to registration.
  • Prior/Concurrent Therapy: Corticosteroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to registration.
  • Prior/Concurrent Therapy: Growth Factors: Off all colony forming growth factor(s) > or = 2 weeks prior to registration (G-CSF, GM-CSF, Erythropoietin).
  • Patients must not have received: cytochrome P450 3A4 (CYP3A4) inhibitors within seven (7) days prior to registration on protocol and for the duration of the study. However, amiodarone, another CYP3A4 inhibitor, should have been discontinued 6 months prior to registration and for the duration of the study.
  • Patient must not have received: CYP3A4 inducers within fourteen (14) days prior to registration and for the duration of the study.
  • Patient must not have received: Cimetidine within 48 hours prior and for the duration of the study.
  • The following laboratory values must be assessed within 7 days prior to registration and must be repeated if initial labs were done greater than (>seven) (7) calendar days prior to the start of therapy. Organ Function: Must have adequate organ function and marrow function as defined by the following parameters: Bone Marrow: Absolute neutrophil count >or =1000microliter, Platelets > or = 100,000 microliter (transfusion independent), Hemoglobin >or =8.0 g/dL. Renal: Serum creatinine <or = 1.5 times upper limit of institutional for age or glomerular filtration rate (GFR)>or = 70ml/min/1.73m2 Hepatic: Total bilirubin < or = 1.5 times upper limit of normal for age: serum glutamate pyruvate transaminase (SGPT) (ALT)<2.5x institutional upper limit of normal for age and albumin > or = 2g/dL. No overt renal, hepatic, cardiac or pulmonary disease.
  • No overt renal, hepatic, cardiac or pulmonary disease.
  • Adequate cardiac function, assessed within 2 weeks prior to registration, defined as: shortening fraction of > or = 27% by echocardiogram, or ejection fracture (LVEF) > or = 50% by gated radionucleotide study.
  • Adequate pulmonary function, assessed within 2 weeks prior to registration, defined as: no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination.
  • Signed informed consent according to institutional guidelines must be obtained.
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 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 and will be removed from the study.
  • Patient must begin therapy within 7 calendar days of registration.

Who cannot join

  • Patients may not have previously been treated with Bevacizumab or Lapatinib.
  • Patients with any significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
  • Patients with any disease that would obscure toxicity or dangerously alter drug metabolism.
  • Patients receiving any other anticancer or experimental drug therapy.
  • Patients with uncontrolled infection.
  • Patients on enzyme inducing anticonvulsants.
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  • Patients with > / = Grade 2 uncontrolled hypertension.
  • History of a stroke, myocardial infarction, or unstable angina in the previous 6 months.
  • Evidence of a bleeding diathesis, coagulopathy or PT international normalized ratio (INR)>1.5.
  • Patients who require the use of therapeutic anti-coagulation: except as required to maintain patency of preexisting permanent vascular catheter.
  • Pre-existing coagulopathy or thrombosis: Patients must not have been previously diagnosed with a deep venous or arterial thrombosis (including pulmonary embolism), and must not have a known thrombophilic condition.
  • Patients must have recovered from any surgical procedure before enrolling on this study.
  • History of an abdominal fistula, GI perforation, or intra-abdominal abscess within previous 6 months.
  • A serious, non healing wound, ulcer, or bone fracture.
  • Evidence of a new intracranial or intratumoral hemorrhage that is larger than a punctuate size on baseline MRI obtained within 14 days prior to study registration.
  • If there is proteinuria present on dipstick, patients must have a 24 hour urine collection. Patients are excluded if they have >500 mg protein on 24 hour urine collection.
  • Pregnancy: Females of childbearing potential must have negative serum or urine pregnancy test within 7 days prior to study entry. The effects of lapatinib on the developing human fetus are unknown. However, bevacizumab is known to be teratogenic and detrimental to fetal development and endometrial proliferation, thereby having a negative effect on fertility.
  • Breastfeeding: Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lapatinib of bevacizumab, breastfeeding should be discontinued if the mother is treated on this study.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Children's Memorial Hospital

    Chicago, Illinois, 60614

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Stanford University Medical Center

    Stanford, California, 94305

Other trials in United States

About this study

Official title: A Phase II Study of Bevacizumab and Lapatinib in Children With Recurrent or Refractory Ependymoma

The goal of this clinical research study is to learn if the combination of Avastin (bevacizumab) and Tykerb (lapatinib) can help to control ependymoma in pediatric patients. The safety of this drug combination will also be studied.

Read the detailed description

The Study Drugs:

Bevacizumab is designed to block the growth of blood vessels that supply nutrients necessary for tumor growth. This may prevent and/or slow down the growth of cancer cells.

Lapatinib is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cells.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive bevacizumab every 2 weeks while you are on study (2 times during each 4-week "study cycle"). The first time you receive the drug, it will be given by vein over 90 minutes. If this dose is well tolerated, you may receive future doses over 30 minutes.

You will take pills of lapatinib 2 times each day while you are on study. The pills should be taken at about the same time each day. You should not eat or drink anything except water for 1 hour before or 1 hour after you take the pills. If you miss a dose, do not take extra pills the next day to try and make up for the missed dose. You should report any missed pills or any trouble you may have with taking the pills to your study doctor.

You will be given a patient diary in which you must record what time you take lapatinib each time.

Study Visits:

At all study visits, you will be asked about any other drugs that you may be taking and about any side effects that you may be experiencing.

During Cycle 1 the following tests and procedures will be performed at least 1 time each week:

  • You will have a physical exam, including measurement of your vital signs.
  • Your performance status will be recorded.

Two (2) times each week during Cycle 1, blood (about 2-3 teaspoons) will be drawn for routine tests.

At the end of Cycle 1, urine will be collected for routine tests.

On Days 1 and 15 of Cycle 2, the following tests and procedures will be performed:

  • You will have a physical exam, including measurement of your vital signs.
  • Your performance status will be recorded.
  • Blood (about 2-3 teaspoons) will be drawn for routine tests.

At the end of Cycle 2, you will have an MRI scan of your head to check the status of the disease. If your doctor thinks it is needed, you will also have an MRI of your spine and a spinal tap to check your cerebrospinal fluid (CSF) for presence of disease.

On Day 1 of Cycle 3 and beyond, the following tests and procedures will be performed:

  • You will have a physical exam, including measurement of your vital signs.
  • Your performance status will be recorded.
  • Blood (about 2-3 teaspoons) and urine will be collected for routine tests.

Every 8 weeks, starting with the end of Cycle 4, while you are on study, the following tests and procedures will be performed:

  • You will have an MRI scan of the brain to check the status of the disease.
  • If your doctor thinks it is needed, you will have an MRI scan of the spine to check the status of the disease.
  • If your doctor thinks it is needed, you will have a spinal tap to check your CSF for the presence of disease.

Every 12 weeks while you are on study, the following tests and procedures will be performed to check for possible side effects:

  • You will have an echocardiogram or a multiple gated acquisition scan (MUGA) (if the study doctor thinks it is necessary) to test your heart function.
  • You will have an x-ray of your right knee.
  • If your doctor thinks it is needed, you will have an MRI scan of both knees.

Length of Study:

You will be on study for up to 2 years. You will be taken off study if the disease gets worse, if you experience intolerable side effects, or if the doctor thinks it is in your best interest.

End-of-Treatment Visit:

After you have finished receiving the study drugs, the following tests and procedures will be performed:

  • You will have a physical exam, including measurement of your vital signs.
  • You will be asked about any other drugs that you may be taking and about any side effects that you may be experiencing.
  • Your performance status will be recorded.
  • Blood (about 2-3 teaspoons) will be collected for routine tests.
  • You will have an echocardiogram or a MUGA scan (if the study doctor thinks it is necessary) to test your heart function.
  • You will have an x-ray of your right knee.
  • You will have MRI scans of the brain and spine to check the status of the disease.
  • If your doctor thinks it is needed, you will have a spinal tap to check the status of the disease.

Long-Term Follow-up:

You will have a follow-up visit 30 days after you have finished receiving the study drugs. The following tests and procedures will be performed:

  • You will have a physical exam, including measurement of your vital signs.
  • You will be asked about any other drugs that you may be taking and about any side effects that you may be experiencing.
  • Your performance status will be recorded.
  • Blood (about 2-3 teaspoons) will be collected for routine tests.

This is an investigational study. Bevacizumab is FDA approved and commercially available for the treatment of colon, rectum, lung and certain types of breast cancer. Lapatinib is FDA approved and commercially available for the treatment of certain types of breast cancer. The use of this drug combination in ependymomas in pediatric patients is investigational.

Up to 40 patients will take part in this multicenter study. Up to 6 patients will be enrolled at MD Anderson.

Being tested
Bevacizumab, Lapatinib
Keywords
Brain Tumor, Recurrent Ependymoma, Refractory Ependymoma, Intracranial ependymoma, Ependymoblastoma, Subependymoma, Myxopapillary, Clear cell, Anaplastic, Bevacizumab, Avastin, Anti-VEGF Monoclonal Antibody, rhuMAb-VEGF, Lapatinib, Tykerb, GW572016
Medical subject headings
Brain Neoplasms, Ependymoma, Neuroectodermal Tumors, Primitive, Glioma, Subependymal

What participants receive

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

  • BevacizumabDrug

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

    10 mg/kg given by vein over 90 minutes for first injection (30-60 minutes for subsequent doses) every 2 weeks while on study (2 times during each 4-week "study cycle").

  • LapatinibDrug

    Also called Tykerb, GW572016

    Pills of 700 mg/m^2/dose given orally 2 times each day.

Study groups in NCT00883688
Study groupRoleWhat they receive
Bevacizumab + LapatinibExperimentalBevacizumab 10 mg/kg given by vein over 90 minutes for first injection (30-60 minutes for subsequent doses) every 2 weeks while on study (2 times during each 4-week "study cycle"). Lapatinib Pills of 700 mg/m^2/dose given orally 2 times each day.
Receives: Drug: Bevacizumab; Drug: Lapatinib

What is being measured

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

  1. Objective Response Rate

    Objective response rate defined as number of participants out of total participants with complete response plus partial response (CR+PR) sustained for at least four weeks. Complete Response (CR) - Complete disappearance on magnetic resonance imaging (MRI) of all enhancing tumor and mass effect, on a stable or decreasing dose of corticosteroids (or receiving only adrenal replacement doses), accompanied by a stable or improving neurologic examination and must be sustained for at least 4 weeks. If cerebrospinal fluid (CSF) for presence of disease was positive it must become negative. Partial Response (PR) - Greater than or equal to 50% reduction in tumor size by bi-dimensional measurement on a stable or decreasing dose of corticosteroids, accompanied by stable or improving neurological examination and must be sustained for at least 4 weeks.

    Measured: 4 weeks following treatment, repeat assessments up to 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 posted20 Apr 2009 (estimated)
  2. Study startJul 2009
  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
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00883688
Sponsor's protocol ID
CERN08-01
Other IDs
NCI-2012-02129
Status last verified
Aug 2020
First submitted
17 Apr 2009
Last updated
26 Aug 2020
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab and Lapatinib in people with Brain Cancer and Pediatric Cancers, run by M.D. Anderson Cancer Center at 6 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 22 inclusion and 18 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 26 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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 26 Aug 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?

Objective Response Rate (time frame: 4 weeks following treatment, repeat assessments up to one 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 NCT00883688.

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 26 Aug 2020.

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