AzTrials
AzTrials

GliomaPhase 2NCT00107003

GW572016 to Treat Recurrent Malignant Brain Tumors

A Phase 2 study testing lapatinib ditosylate, Adjuvant therapy and Conventional surgery in people with Glioma and Brain Tumor, run by National Cancer Institute (NCI) 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

This study will examine whether an experimental drug called GW572016 can delay tumor growth in patients with glioblastoma multiforme (GMB, a malignant brain tumor). GW572016 is believed to affect cancer cell function by interfering with the internal signaling needed for the cancer to grow. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioma, Brain Tumor, Glioblastoma Multiforme
What is being tested?
lapatinib ditosylate, Adjuvant therapy and Conventional surgery
Type of treatment
Surgery or procedure
How many people
9 participants
Where
1 siteUnited States
Study dates
30 Mar 2005to 30 Nov 2012
Phase
Phase 2
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 with histologically proven intracranial tumors to include only glioblastoma multiforme (GBM) and Gliosarcoma (GS). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a GBM is made.
  • Unstained slides (at least 5, but prefer 10) or 1 tissue block must be available from at least one prior surgery. If available, frozen tissue is also requested from earlier surgeries.
  • Patients must be candidates for surgical re-resection (total, or sub-total) in order to be eligible for this study. Following surgery, a scan should be done no later than 96 hours.
  • Patients may be on a non-enzyme-inducing anti-epileptic drugs (Non-EIAED's). They may not be on EIAED's. If previously on an EIAED, patient must be off of it for two weeks prior to initiation of pre-operative drug.
  • Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA scan (within 42 days of registration).
  • All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information. Patients must be registered in the NABTC database prior to treatment with study drug.
Show all 16Show fewer
  • Patients must be greater than or equal to 18 years old, and with a life expectancy greater than 8 weeks.
  • Patients must have a Karnofsky performance status of greater than or equal to 60.
  • Patients must have recovered from the toxic effects of prior therapy and at least 28 days from any investigational agent, 28 days from prior cytotoxic therapy, 28 days from radiation, 14 days from vincristine, 42 days from nitrosoureas, 21 days from procarbazine administration, and 7 days from non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair.
  • Patients must have adequate bone marrow function (WBC greater than or equal to 3,000/microl, ANC greater than or equal to 1,500/mm(3), platelet count of greater than or equal to 100,000/mm(3), and hemoglobin greater than or equal to 10 gm/dl), adequate liver function (SGOT and bilirubin less than 2.5 times ULN), and adequate renal function (creatinine less than 1.5 mg/dL 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 shown unequivocal evidence for tumor progression by MRI or CT scan. Stable dose of steroids is not mandated for this study. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement.
  • Patients must have failed prior radiation therapy.
  • Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium scanning, MR spectroscopy or surgical documentation of disease.
  • Patients may have had treatment for no more than 2 prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation+/- chemo [which includes gliadel wafers] if that was used as initial therapy). The intent therefore is that patients had no more than 3 prior therapies (initial and treatment for 2 relapses). If the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse. For patients who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse.
  • Eligibility to restart drug post-op.
  • Patients must agree to practice adequate contraception. Women of childbearing potential must have a negative B-HCG pregnancy test documented within 7 days prior to registration.

Who cannot join

  • Patients may not be on any medications listed in section 3.2.1
  • Patients must not have 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 a history of any other cancer (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.
  • Patients must not have active infection or serious intercurrent medical illness.
  • Women of childbearing potential must not be pregnant/breast feeding. Patients must not be pregnant because no studies with this drug have been performed to evaluate safety.
  • HIV-Positive patients receiving combination anti-retroviral therapy are excluded from the study due to possible retro-viral drug interactions.
  • Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.
  • Patients must not have received prior therapy with Signal transduction inhibitors (e.g. ZD1839, OSI-774, R115777)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Biomarker and Phase II Study of GW572016 in Recurrent Malignant Glioma

This study will examine whether an experimental drug called GW572016 can delay tumor growth in patients with glioblastoma multiforme (GMB, a malignant brain tumor). GW572016 is believed to affect cancer cell function by interfering with the internal signaling needed for the cancer to grow. The study will also determine whether the presence of specific proteins in the tumor can predict what effects GW572016 will have on the tumor.

Patients 18 years of age and older with GMB whose brain tumor does not respond to standard medical treatment and who can undergo surgery for their tumor may be eligible for this study. Candidates are screened with a physical examination and neurocognitive examination, blood tests, electrocardiogram (EKG), echocardiogram (ultrasound test of heart function) or MUGA scan (nuclear medicine test of heart function), magnetic resonance imaging (MRI) of the head, and computed tomography (CT) of the head. CT uses x-rays and MRI uses a magnetic field and radio waves to show brain structure.

Read more

Participants undergo the following tests and procedures:

  • MRI and blood tests before surgery.
  • Surgery to remove the brain tumor.
  • Follow-up MRIs every 8 weeks after surgery.
  • Follow-up echocardiograms or MUGA scans every 8 weeks after surgery.
  • GW572016 treatment starting 7-10 days before surgery and continuing until the patient or doctor decides it is in the patient's best interest to stop it or until the tumor worsens. (The drug is stopped temporarily for surgery and a healing period after surgery.)
  • Blood tests every 2 weeks to evaluate the effects of GW572016 on the body.
  • Blood test before the first GW572016 treatment and at the time of surgery to assess the effect of the drug on the cells and to determine how much drug is present in the blood at the time of surgery.

Participants are followed in clinic at least monthly while taking GW572016. While on treatment they keep a diary documenting their daily treatments. The diary is collected at the monthly follow-up exams. After the treatment ends, patients are contacted periodically by the research staff for the rest of their lives to follow the long-term effects of the study.

Read the detailed description

Background:

  • One of the most critical challenges facing glioblastoma translational research is developing ways to predict, based on a patient's biopsy, which targeted inhibitor is most likely to provide benefit. The studies outlined in this proposal are designed to determine which glioblastoma patients are most likely to benefit from GW572106, and may provide a blueprint for analyzing promising new pathway inhibitors in the future. We anticipate that these studies will serve as the basis for biological endpoint based trials in the future. Thus, the overall goal is to evaluate the efficacy of GW572016 in the treatment of recurrent malignant gliomas in patients who are candidates for re-resection.

Objective:

  • Determine the 6-month progression-free survival rate for patients with recurrent or progressive glioblastoma treated with GW572016.
  • Determine whether GW572016 inhibits the phosphorylation of its cellular targets EGFR and HER2, and the downstream PI3K-AKT and RAS-ERK signaling pathways in glioblastoma patients in vivo.
  • Determine tumor concentrations of GW572016.
  • Assess overall progression free survival and safety.

Eligibility:

  • Patients with histologically proven intracranial tumors to include only glioblastoma multiforme (GBM) and Gliosarcoma (GS). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a GBM is made.
  • Patients must be candidates for surgical re-resection (total, or sub-total) in order to be eligible for this study. Following surgery, a scan should be done no later than 96 hours
  • Patients may be on a non-enzyme-inducing anti-epileptic drugs (Non-EIAED's). They may not be on EIAED's. If previously on an EIAED, patient must be off of it for two weeks prior to initiation of pre-operative drug.

Design:

  • A Pre-Treatment blood sample (10ml) will be obtained in all patients for genotyping
  • Pre- Operative: GW572016 will be administered at a starting dose of 750 mg orally BID daily on an outpatient basis for 7-10 days. (This range is to allow flexibility for planning surgery). GW572016 will be continued up to and including the evening before surgery.
  • At the time of surgery 10ml of blood will be collected in EDTA containing tubes for pharmacodynamic analysis
  • Treatment may be instituted postoperatively as soon as patients have recovered from effects of surgery and demonstrated wound healing. Treatment with GW572016 post-operatively should start no later than 28 days after surgery. GW572016 will be administered at a starting dose of 750 mg orally BID daily on an outpatient basis. GW572016 will be administered continuously; however, for the purposes of protocol evaluations, a cycle will be defined as 28 days.
Being tested
lapatinib ditosylate, Adjuvant therapy, Conventional surgery, Neoadjuvant therapy
Keywords
Brain, Tumor, Surgery, Therapy, Trial, Brain Tumor, Glioblastoma Multiforme, GBM, Gliosarcoma, GS
Medical subject headings
Glioma, Brain Neoplasms, Glioblastoma, Gliosarcoma, Neoplasms

What participants receive

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

What is being measured

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

  1. Determine 6-month progression-free survival of patients undergoing surgery for recurrent progressive glioblastoma multiforme or gliosarcoma treated with lapatinib.

Timeline

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

  1. First posted4 Apr 2005 (estimated)
  2. Study start30 Mar 2005
  3. Primary completion5 Dec 2007
  4. Study completion30 Nov 2012

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
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00107003
Sponsor's protocol ID
050134
Other IDs
05-C-0134
Status last verified
30 Nov 2012
First submitted
2 Apr 2005
Last updated
5 Jul 2018
Results posted
No

Publications

  • Burgess AW, Cho HS, Eigenbrot C, Ferguson KM, Garrett TP, Leahy DJ, Lemmon MA, Sliwkowski MX, Ward CW, Yokoyama S. An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Mol Cell. 2003 Sep;12(3):541-52. doi: 10.1016/s1097-2765(03)00350-2.

    PubMed 14527402

  • Choe G, Park JK, Jouben-Steele L, Kremen TJ, Liau LM, Vinters HV, Cloughesy TF, Mischel PS. Active matrix metalloproteinase 9 expression is associated with primary glioblastoma subtype. Clin Cancer Res. 2002 Sep;8(9):2894-901.

    PubMed 12231534

  • Hendriks BS, Opresko LK, Wiley HS, Lauffenburger D. Quantitative analysis of HER2-mediated effects on HER2 and epidermal growth factor receptor endocytosis: distribution of homo- and heterodimers depends on relative HER2 levels. J Biol Chem. 2003 Jun 27;278(26):23343-51. doi: 10.1074/jbc.M300477200. Epub 2003 Apr 9.

    PubMed 12686539

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing lapatinib ditosylate, Adjuvant therapy and Conventional surgery in people with Glioma and Brain Tumor, run by National Cancer Institute (NCI) 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 16 inclusion and 8 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 5 Jul 2018. 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?

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?

Determine 6-month progression-free survival of patients undergoing surgery for recurrent progressive glioblastoma multiforme or gliosarcoma treated with lapatinib.. 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 NCT00107003, which also lists 3 linked publications.

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 5 Jul 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in