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Updated: Jul 16, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Phase I study of sorafenib and tipifarnib for recurrent glioblastoma: NABTC 05-02
Phioanh Leia Nghiemphu1, Victoria Asuquo Ebiana2,3, Patrick Wen4
1Department of Neurology, University of California, Los Angeles, 710 Westwood Plaza, Reed 1-230, Los Angeles, CA, 90230, USA. leian@ucla.edu.
Abstract:
Recurrent glioblastoma (GBM) has a very low 6-month progression free survival (PFS) with currently available treatments. Combination chemotherapy to target multiple cell signaling pathways is currently being investigated in order to improve prognosis for recurrent disease. The purpose of this phase I study was to determine the maximum tolerated dose (MTD) for the combination of tipifarnib and sorafenib for the treatment of recurrent GBM. Patients with pathologically proven WHO grade IV GBM and radiographically proven tumor recurrence were eligible for this study. Treatments included sorafenib at twice daily and escalating dosages of tipifarnib. Dose-limiting toxicity (DLT) was determined over the first 28-days of treatments, and the MTD was determined in a 3 + 3 study design. We enrolled 24 patients, and 21 patients completed the MTD period. The study was stopped early with no MTD determination for excessive toxicities. The last dose level reached was sorafenib at 200 mg twice a day and tipifarnib 100 mg twice a day on an alternating week schedule. The DLTs included diarrhea, lipase elevation, hypophosphatemia, and arthralgia. The combination of sorafenib and tipifarnib has excessive toxicities and full single agent dosages could not be achieved in combination.
Insights
Combination therapy with tipifarnib and sorafenib for recurrent glioblastoma showed excessive toxicities. The maximum tolerated dose could not be determined due to dose-limiting toxicities in this phase I study.
Area of Science:
- Neuro-oncology
- Clinical Pharmacology
- Cancer Treatment
Background:
- Recurrent glioblastoma (GBM) presents a significant challenge with poor prognosis and limited treatment options.
- Combination chemotherapy targeting multiple cell signaling pathways is a strategy to improve outcomes for recurrent GBM.
- Existing treatments offer very low 6-month progression-free survival (PFS) for recurrent disease.
Purpose of the Study:
- To determine the maximum tolerated dose (MTD) of combining tipifarnib and sorafenib in patients with recurrent GBM.
- To evaluate the safety and tolerability of escalating doses of tipifarnib combined with a fixed dose of sorafenib.
Main Methods:
- Phase I clinical trial employing a 3+3 study design.
- Patients with pathologically and radiographically confirmed recurrent WHO grade IV GBM were enrolled.
- Treatment involved twice-daily sorafenib with escalating twice-daily doses of tipifarnib on an alternating week schedule; dose-limiting toxicities (DLTs) were assessed over 28 days.
Main Results:
- The study enrolled 24 patients; 21 completed the MTD assessment period.
- The trial was terminated early due to excessive toxicities, preventing MTD determination.
- The highest dose level reached was sorafenib 200 mg twice daily and tipifarnib 100 mg twice daily (alternating weeks); DLTs included diarrhea, lipase elevation, hypophosphatemia, and arthralgia.
Conclusions:
- The combination of tipifarnib and sorafenib demonstrated excessive toxicities at the tested dose levels.
- Full single-agent doses could not be safely achieved when these drugs were administered in combination.
- This combination therapy is not considered feasible for treating recurrent glioblastoma due to safety concerns.
