Phase I/II Evaluation of Temozolomide and ZARNESTRA (R115777) for Recurrent and Progressive Glioblastoma Multiforme

NCT00050986 | Completed Phase 1 Results

• 1 other identifier: ID02-126
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest safe dose of the new drug ZARNESTRA (R115777) and temozolomide that can be given to patients with brain tumors (glioblastoma multiforme, GBM). The second goal is to learn if these drugs given in combination can shrink or slow the growth of brain tumors. The safety of this treatment will also be studied.

Conditions

Glioblastoma Multiforme

Keywords

Brain Neoplasms; CNS Diseases; Glioblastoma Multiforme; Temozolomide; Temodar; R115777; Zarnestra

Outcome Measures

Primary Outcomes (1)

• Maximal Tolerating Dose (MTD for Phase I)

  Phase I Dose limiting toxicity evaluation at end of first cycle based on blood tests every two weeks and participants' subjective and objective symptoms. Start Dose Level 100 mg/m² Temozolomide once daily + 400 mg ZARNESTRA twice daily; Dose Level 1 100 mg/m² Temozolomide once daily + 500 mg ZARNESTRA twice daily; Dose Level 2 150 mg/m² Temozolomide once daily + 500 mg ZARNESTRA twice daily; Dose Level 3 150 mg/m² Temozolomide once daily + 600 mg ZARNESTRA twice daily; Dose Level 4 150 mg/m² Temozolomide once daily + 800 mg ZARNESTRA twice daily

  End of first cycle (4 weeks) evaluation

Secondary Outcomes (1)

• Progression-free Survival (Phase II)

  6 months

Study Arms (1)

Temozolomide and R115777

EXPERIMENTAL

Drug: Temozolomide; Drug: R115777

Interventions

Temozolomide DRUG

Starting Dose Level: 100 mg/m\^2 taken by mouth once daily for 7 days, followed by 7 days rest and another 7-day dosing period and 7-day rest period.

Also known as: Temodar

Temozolomide and R115777

R115777 DRUG

Starting Dose Level: 400 mg taken by mouth for 7 consecutive days every other week on alternating weeks (days 8-14 and 22-28) every 4 weeks.

Also known as: Zarnestra

Temozolomide and R115777

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically proven supratentorial glioblastoma multiforme (GBM).
• 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 primary investigator to document tumor volume changes to provide a gross assessment of growth rate.
• Patients may have had: a) no prior chemotherapy, b) 1 prior adjuvant chemotherapy, c) 1 prior adjuvant chemotherapy followed by 1 regimen for recurrent disease, or d) 1 or 2 prior chemotherapy regimens for recurrent or progressive tumor.
• 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.
• 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 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.
• Pts with recent resection of recurrent or progressive tumor will be eligible if all of the following conditions apply: Pt has recovered from the effects of surgery; Residual disease after resection of recurrent tumor is not mandated for eligibility. To assess the extent of residual disease post-operatively, a CT/MRI should be done no later than 96 hours post-operatively or at least 4 weeks post-operatively, and within 14 days before registration. If steroid dose increased between the day of imaging and registration, a new baseline scan is required after stable steroids for 5 days.
• Patients must have a Karnofsky performance status of \>/= 60
• 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.
• Patients must have adequate bone marrow function (ANC\>/= 1,500/mm(3) and platelet count of \>/= 100,000/mm(3)), adequate liver function (SGPT and SGOT \</= 2.5 times normal, bilirubin \</= 2 mg%), and adequate renal function (BUN and creatinine \<1.5 times institutional normal) prior to starting therapy.
• ZARNESTRA may interfere with coumadin dosing and patients who are taking this combination will require more frequent monitoring of their PT, PTT and INR.
• Patient has no risk factors for HIV or is serologically negative.

You may not qualify if:

• Patients must not be taking primidone, carbamazepine, phenobarbital or phenytoin anticonvulsants. Patients changing from these anticonvulsants to others that are allowed must be off the drugs listed above for at least 1 week.
• Patients must not be taking cimetidine, erythromycin azole antifungals, paclitaxel, tacrolimus or cyclosporine.
• Patients must not have uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, myocardial infarction within the previous six months, or serious uncontrolled cardiac arrhythmia.
• Because of the concerns of potentially harmful interactions of ZARNESTRA and other medications taken by patients who are HIV positive or have AIDS related diseases, patients who are HIV positive will not be eligible for entry into this study. Only patients with suspected HIV will be tested and if positive, will be ineligible.
• 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.
• Patients must not have: a) active infection b) disease that will obscure toxicity or dangerously alter drug metabolism c) serious intercurrent medical illness. d) prior recurrence with either Temozolomide or a farnesyl transferase inhibitor.
• Patients must not be pregnant and must practice adequate contraception

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Johnson & Johnson: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Central Nervous System Diseases

Interventions

Temozolomide; tipifarnib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: W.K. Yung,MD/Clinical Professor, Neuro-Oncology
• Organization: University of Texas, M. D. Anderson Cancer Center

wyung@mdanderson.org

(713) 794-1285

Study Officials

• Mark R. Gilbert

  MDAnderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 31, 2002
• First Posted: January 3, 2003
• Study Start: December 1, 2002
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: September 22, 2020
• Results First Posted: September 16, 2010

Record last verified: 2020-09

Locations

US (1)