Sarasar and Temodar for Glioblastoma Multiforme Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00102648
First received: January 31, 2005
Last updated: July 8, 2013
Last verified: July 2013

January 31, 2005
July 8, 2013
December 2004
December 2014   (final data collection date for primary 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. [ Time Frame: 4 Years ] [ Designated as safety issue: Yes ]
  • To determine the maximum tolerated dose Sarasar (SCH66336, lonafarnib) when combined with Temodar (temozolomide) in an alternating week schedule
  • To describe the toxicities of the Sarasar and Temodar combination treatment using this dosing schedule
  • To evaluate response as measured by 6-month progression-free survival and objective tumor response
Complete list of historical versions of study NCT00102648 on ClinicalTrials.gov Archive Site
To learn if these drugs given in combination can shrink or slow the growth of brain tumors. [ Time Frame: 4 Years ] [ Designated as safety issue: No ]
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Sarasar and Temodar for Glioblastoma Multiforme Patients
Phase I/Ib Study of Sarasar and Temodar in Patients With Recurrent or Temodar-Refractory Glioblastoma Multiforme

The goal of this clinical research study is 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. The second goal is to learn if these drugs given in combination can shrink or slow the growth of brain tumors.

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.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Glioblastoma Multiforme
  • Gliosarcoma
  • Brain Tumors
  • Drug: Sarasar
    Starting dose 100 mg by mouth twice a day, with water, for 7 consecutive days (days 8 through 14 and days 22 through 28). Cycle is 28 days.
    Other Names:
    • Lonafarnib
    • SCH 66336
  • Drug: Temodar
    150 mg/m^2 by mouth once a day, after fasting one hour, for 7 consecutive days (days 1 through 7 and days 15 through 21). Cycle is 28 days.
    Other Name: Temozolomide
Experimental: Sarasar + Temodar

Sarasar Starting Dose: 100 mg by mouth twice a day, with water, for 7 consecutive days (days 8 through 14 and days 22 through 28). Cycle is 28 days.

Temodar 150 mg/m^2 by mouth once a day, after fasting one hour, for 7 consecutive days (days 1 through 7 and days 15 through 21). Cycle is 28 days.

Interventions:
  • Drug: Sarasar
  • Drug: Temodar
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
35
Not Provided
December 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Patients with histologically proven supratentorial glioblastoma multiforme (GBM) or gliosarcoma.
  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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00102648
2004-0424, SPRI # P04084
No
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
Schering-Plough
Principal Investigator: Mark R. Gilbert, MD M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP