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Phase I/Ib Study of Sarasar and Temodar in Patients With Recurrent or Temodar-Refractory Glioblastoma Multiforme

Phase 1
18 Years
Open (Enrolling)
Glioblastoma Multiforme, Gliosarcoma, Brain Tumors

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Trial Information

Phase I/Ib Study of Sarasar and Temodar in Patients With Recurrent or Temodar-Refractory Glioblastoma Multiforme

Temozolomide is a chemotherapy drug that works by attacking cancer cells, causing them to
die. Lonafarnib is a new drug that may slow down the growth of cancer cells. Used in
combination, the two drugs may control the growth of brain tumors.

If you are eligible to take part in the study, you will be given temozolomide and lonafarnib
as treatment. The size of study drug doses being given will increase after every 3
participants are enrolled on the study, until the highest safe dose of each drug, when given
in combination, is found.

If you are enrolled on the Phase Ib part of this study, you will be treated at the highest
tolerable dose that was found in the Phase I part of the study. You will receive this dose
of temozolomide on a 7-day on, 7-day off schedule. You will also receive Sarasar by mouth
twice a day using a 7-day on, 7-day off schedule.

Temozolomide and lonafarnib will be taken by mouth in this study. You will take
temozolomide once a day for 7 days every other week (Days 1-7 and 15-21). You must not eat
for 1 hour before and after taking the drug; drinking water is allowed. During the
alternate weeks (Days 8-14 and 22-28), you will take the lonafarnib tablet by mouth in the
morning and evening, with water. You should not eat grapefruit or drink grapefruit juice
while you are taking the study medication as this will affect how study medication is broken
down in your body. This will be repeated every 28 days (1 study course). All treatment may
be given on an outpatient basis, and so you will not require a hospital stay.

You may keep on taking temozolomide and lonafarnib for up to 24 courses (about 2 years).
You will be taken off study if the disease gets worse or intolerable side effects occur.
You may not receive any other treatment for cancer (including surgery) while taking part in
this study.

You will come to the clinic to have a complete physical exam before each course of
treatment. You will have a neurological exam within 14 days before every odd-numbered course
(3, 5, 7, etc), or at any time that the doctor feels it is needed. Blood counts (about 1
teaspoon) will be done before every course of treatment and on Day 22 of each course.
Blood chemistry tests and anticonvulsant levels, if applicable, (less than 1 tablespoon)
will be repeated before each course of treatment. An MRI scan will be done before the
odd-numbered (3, 5, 7, etc.) courses of treatment, or at any time that the doctor feels it
is needed. Patients taking the blood thinner warfarin will have blood tests (less than 1
teaspoon) more often to check the effects of the drug.

Your doctor may decide to take you off combination treatment before 2 years and give you
only the lonafarnib alone. If you continue to receive lonafarnib by itself without the
addition of temozolomide, after having received a minimum of 1 year of the combination
therapy, you will have routine blood (about 2-3 teaspoons) tests every 4 weeks and an MRI
with clinic follow-up for physical and neurological exams every 3 months while receiving
continuation treatment.

When you have finished the study treatment, you will have another complete physical and
neurological exam. Blood tests (less than 2 tablespoons of blood) will be performed. Another
MRI scan will be done.

This is an investigational study. Temozolomide is approved by the FDA for the treatment of
some brain tumors. Lonafarnib is approved for research use only in the treatment of brain
tumors. The use of these two drugs together is experimental. About 35 patients will take
part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients with histologically proven supratentorial glioblastoma multiforme (GBM) or

2. Patients must have shown unequivocal evidence for tumor recurrence or progression by
MRI scan after radiation therapy. The scan done prior to study entry documenting
progression will be reviewed by the treating physician to document tumor volume
changes to provide a gross assessment of growth rate.

3. Patients may have had as many as 2 prior chemotherapy regimens for recurrent or
progressive tumor. Patients must have had prior treatment with Temodar but may not
have had prior treatment with farnesyl transferase inhibitors (Sarasar or Zarnestra).
Patients in phase 1b expansion are required to have received a minimum of two cycles
of adjuvant TMZ.

4. All patients must sign an informed consent indicating that they are aware of the
investigational nature of this study in keeping with the policies of this hospital.

5. Patients must have shown unequivocal evidence for tumor progression by MRI or CT
scan. A scan should be performed within 14 days prior to registration and on a
steroid dose that has been stable or decreasing for at least 5 days. If the steroid
dose is increased between the date of imaging and registration a new baseline MR/CT
is required. The same type of scan, i.e., MRI or CT must be used throughout the
period of protocol treatment for tumor measurement.

6. Pts having had recent resection of recurrent or progressive tumor are eligible as
long as: a) Patients must be status post surgical resection at least 2 weeks prior to
study enrollment, have recovered from surgery, have adequate early wound healing and
a Karnofsky performance status of > or = 60.

7. Continued from Inclusion #6. b) Residual disease following resection of recurrent
tumor is not mandated for eligibility into the study. A CT/ MRI should be done within
96 hrs post-op or at least 4 wks post-op (within 14 days of registration). If the
steroid dose is increased between the scan date and registration, a new baseline
MRI/CT is required on a stable steroid dose for 5 days.

8. Patients must be >/= 18 years of age.

9. Patients must have a Karnofsky performance status of >/= 60.

10. Patients must have recovered from the toxic effects of prior therapy: 4 weeks from
prior cytotoxic therapy and/or at least two weeks from vincristine, 6 weeks from
nitrosoureas, 3 weeks from procarbazine administration, and 1 week for 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.

11. Patients must have adequate bone marrow function (ANC >/= 1,500/mm3 and platelet
count of >/= 100,000/mm3), adequate liver function (SGPT and alkaline phosphatase
<2.5 times normal, bilirubin <1.5 mg%), and adequate renal function (BUN and
creatinine <1.5 times institutional normal) prior to starting therapy.

Exclusion Criteria:

1. Patients must not be taking primidone, carbamazepine, phenobarbital or phenytoin
anticonvulsants. Patients changing from these anticonvulsants to other allowable
drugs that are not enzyme inducing anti-epileptic drugs (EIAEDs) must be off the
drugs listed above for at least 72 hours prior the initiation of treatment.

2. Patients with a history of any other cancer (except non-melanoma skin cancer or
carcinoma in-situ of the cervix), are ineligible unless in complete remission and off
of all therapy for that disease for a minimum of 3 years.

3. Patients must not have: a) uncontrolled active infection b) disease that will obscure
toxicity or dangerously alter drug metabolism c) serious intercurrent medical
illness. d) prior recurrence with a farnesyl transferase inhibitor e) oral
contraceptives and other hormonal methods (Depo-Provera) of birth control.

Type of Study:


Study Design:

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

Outcome Measure:

To find the highest safe dose of the new drug Sarasar (lonafarnib) that can be given together with Temodar (temozolomide) in a continuous daily dosing regimen to patients with brain tumors.

Outcome Time Frame:

4 Years

Safety Issue:


Principal Investigator

Mark R. Gilbert, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 2004

Completion Date:

Related Keywords:

  • Glioblastoma Multiforme
  • Gliosarcoma
  • Brain Tumors
  • Glioblastoma Multiforme
  • Gliosarcoma
  • Brain Tumors
  • Sarasar
  • Temodar
  • Temozolomide
  • Lonafarnib
  • SCH 66336
  • Brain Neoplasms
  • Glioblastoma
  • Gliosarcoma



UT MD Anderson Cancer Center Houston, Texas  77030