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Phase I Trial of R115777 With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

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Trial Information

Phase I Trial of R115777 With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme


PRIMARY OBJECTIVES:

I. Establish MTD for R115777 in combination with Temozolomide with radiation in patients not
on EIAEDs.

II. To define the safety of R115777 in combination with Temozolomide with radiation in this
patient population.

III. To assess for evidence of antitumor activity in this patient population.

OUTLINE: This is a multicenter, dose-escalation study of tipifarnib. Patients are stratified
according to concurrent use of enzyme-inducing antiepileptic drugs (yes [closed to accrual
as of 3/15/05] vs no).

COMBINATION THERAPY: Patients receive oral tipifarnib twice daily on days 1-21. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity. Within
5-9 days after beginning tipifarnib, patients receive oral temozolomide once daily for 6
weeks and concurrently undergo partial brain radiotherapy daily 5 days a week for 6 weeks.
After completion of radiotherapy, patients proceed to adjuvant therapy.

Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are
treated at the MTD.

ADJUVANT THERAPY: Patients continue to receive tipifarnib as above. With the initiation of
the next planned course of tipifarnib, patients receive oral temozolomide on days 1-5.
Treatment repeats every 28 days for 12 courses OR 1 year (whichever is longer) in the
absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients with progressive disease are followed at 10
weeks and then every 4 months. Patients who complete therapy are followed every 2 months for
1 year, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months
thereafter until disease progression.


Inclusion Criteria:



- Patients will have histologically proven intracranial Glioblastoma Multiforme (GBM)
or gliosarcoma (GS)

- Diagnosis will have been established by biopsy or resection within 4 weeks prior to
registration

- Patients must not have received previous radiotherapy to the brain

- Patients must not have received cytotoxic drug therapy, non-cytotoxic drug therapy,
or experimental drug therapy directed against the brain tumor; patients who received
Gliadel wafers will be excluded; patients may have received or be receiving
corticosteroids, non-EIAEDs, analgesics, and other drugs to treat symptoms or prevent
complications

- Cranial MRI or contrast CT must have been performed within 21days of study entry; the
use of MRI rather than CT is preferred; the same type of scan, i.e., MRI or CT must
be used throughout the period of protocol treatment for tumor measurement; if the
surgical procedure was a resection, cranial MRI or contrast CT performed with 96
hours of resection is preferred but not required; patients without measurable or
assessable disease are eligible

- Patients must have a plan to begin partial brain radiotherapy within 5-9 days after
beginning R115777, and within 35 days (5 weeks) of the surgical procedure that
established the diagnosis; radiotherapy must be given at the Radiation Oncology
Department of the registering ABTC institution; radiotherapy must be given by
external beam to a partial brain field in daily fractions of 2.0 Gy, to a planned
total dose to the tumor of 60.0 Gy; stereotactic radiosurgery and brachytherapy will
not be allowed

- Patients must be willing to forego other drug therapy against the tumor while being
treated with R115777 and temozolomide

- All patients must sign an informed consent indicating that they are aware of the
investigational nature of this study; patients must sign an authorization for the
release of their protected health information; patients must be registered with the
Adult Brain Tumor Consortium Central Office (ABTC CO) prior to treatment with study
drug

- Life expectancy > 8 weeks

- Patients must have a Karnofsky performance status of >= 60

- Patients must have adequate bone marrow function and the test must be performed
within 14 days prior to registration; eligibility level for hemoglobin may be reached
by transfusion

- WBC >= 3,000/┬Ál

- ANC >= 1,500/mm^3

- Platelet count of >= 100,000/mm^3

- Hemoglobin >= 10 gm/dl

- Patients must have adequate liver function and the test must be performed within 14
days prior to registration

- SGOT < 2 times ULN

- Bilirubin < 2 times ULN

- Patients must have adequate renal function before starting therapy and the test must
be performed within 14 days prior to registration

- Creatinine < 1.5 mg/dL

- 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 must not have any disease
that will obscure toxicity or dangerously alter drug metabolism

- 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

- 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

- Patients must not have active infection

- Women must not be pregnant or Breast-feeding, and women with reproductive potential
must practice adequate contraception; the anti-proliferative effects of the
investigational agent may be detrimental to the developing fetus or nursing infant

- Patients must not be on chronic coumadin therapy for prior medical problems (e.g.
cardiac valve prophylaxis); this is due to a presumed interaction with coumadin and
ZARNESTRA leading to a significant increase in INR; patients who develop or have
recently developed a deep venous thrombosis or pulmonary embolism who are on or will
take coumadin will be allowed to participate; however, the investigator should be
prepared to monitor patients INR closely

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD of tipifarnib

Outcome Description:

Safety variables will be summarized by descriptive statistics. Adverse events that occur will be reported for each dose level and described in terms of incidence and severity. Laboratory data will be presented by dose level at each observation time. Values outside of normal limits will be identified and their frequency calculated. Parameters will be described based on the CTCAE severity grading. Distribution by CTCAE severity grade (when applicable) and clinical relevance will be given.

Outcome Time Frame:

Week 10

Safety Issue:

Yes

Principal Investigator

Timothy Cloughesy

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03106

NCT ID:

NCT00049387

Start Date:

September 2002

Completion Date:

Related Keywords:

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Glioblastoma
  • Gliosarcoma

Name

Location

Adult Brain Tumor Consortium Baltimore, Maryland  21231-1000