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


Phase 2
18 Years
N/A
Not Enrolling
Both
Glioma, Brain Tumor, Glioblastoma Multiforme, GBM, Gliosarcoma, GS

Thank you

Trial Information

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


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.

Inclusion Criteria


- INCLUSION CRITERIA (General):

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.

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.

EXCLUSION CRITERIA (General):

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)

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Principal Investigator

Elise C Kohn, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

050134

NCT ID:

NCT00107003

Start Date:

March 2005

Completion Date:

November 2012

Related Keywords:

  • Glioma
  • Brain Tumor
  • Glioblastoma Multiforme
  • GBM
  • Gliosarcoma
  • GS
  • Brain
  • Tumor
  • Surgery
  • Therapy
  • Trial
  • Brain Tumor
  • Glioblastoma Multiforme
  • GBM
  • Gliosarcoma
  • GS
  • Brain Neoplasms
  • Glioblastoma
  • Glioma
  • Gliosarcoma

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892