Lonafarnib + Temozolomide for Glioblastoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: Temozolomide

Must not be taking: Primidone, Carbamazepine, Phenobarbital, Phenytoin

Disqualifiers: Other cancer, Uncontrolled infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the side effects of combining two drugs, lonafarnib and temozolomide, for treating glioblastoma, a type of brain cancer. Researchers seek to evaluate whether this combination more effectively stops tumor growth, particularly in cases where glioblastoma has recurred or did not respond to previous treatment with temozolomide alone. Individuals whose glioblastoma has returned or progressed after treatment and who have previously received temozolomide may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain anticonvulsants like primidone, carbamazepine, phenobarbital, or phenytoin at least 72 hours before starting treatment. For other medications, the protocol does not specify, so it's best to discuss with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of lonafarnib and temozolomide has been tested for safety in people. Studies have found that temozolomide can be safely used with a drug like lonafarnib. Importantly, no deaths related to the treatment occurred in these studies, suggesting that the combination is generally well-tolerated. However, these studies remain in the early stages, focusing on finding the best dose and monitoring for side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of lonafarnib and temozolomide for glioblastoma because it targets the disease in a unique way. Most treatments for glioblastoma, like surgery, radiation, and chemotherapy with temozolomide alone, aim to remove or directly attack the tumor cells. However, lonafarnib adds a new dimension by inhibiting a protein involved in cell growth, which may enhance the effectiveness of temozolomide. This dual approach could potentially slow tumor progression more effectively than current options.

What evidence suggests that this treatment might be an effective treatment for glioblastoma?

Research has shown that using lonafarnib with temozolomide may help treat glioblastoma, a type of brain cancer. In this trial, participants will receive a combination of these two drugs. Lonafarnib alone can slightly slow tumor growth, but it proves more effective when combined with temozolomide. Studies have demonstrated that this combination yields better results than using either drug alone. For instance, about 38% of patients did not experience disease progression after six months, which is encouraging. While more research is needed, these early findings suggest that this combination could benefit some patients with glioblastoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Vinay Puduvalli, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with a specific brain cancer called glioblastoma multiforme or gliosarcoma that has returned or didn't respond to temozolomide. Participants must have had prior treatment with temozolomide, can have up to two previous chemotherapy regimens, and need a stable health status (Karnofsky performance >60). They should not have used farnesyl transferase inhibitors before.

Inclusion Criteria

I've had a scan within the required time after surgery, without increasing my steroid dose.

I have recovered from side effects of my last cancer treatment as per the specified time frames.

I have been diagnosed with a specific type of brain tumor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive temozolomide orally once daily on days 1-7 and 15-21 and lonafarnib orally twice daily on days 8-14 and 22-28. Treatment repeats every 28 days for up to 24 courses.

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion every 3 months.

Up to 11 years

What Are the Treatments Tested in This Trial?

Interventions

• Lonafarnib
• Temozolomide

Trial Overview The trial tests the combination of lonafarnib and temozolomide on recurrent or resistant glioblastoma multiforme. It aims to find the safest dose of lonafarnib when combined with temozolomide and assess how effectively this duo can kill tumor cells by blocking cell growth enzymes and stopping cell division.

How Is the Trial Designed?

Group I: Treatment (temozolomide and lonafarnib) Experimental Treatment 2 Interventions

Patients receive temozolomide PO QD on days 1-7 and 15-21 and lonafarnib PO BID on days 8-14 and 22-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase II trial involving 46 patients with progressive low-grade glioma, Temozolomide (Temodar) demonstrated a 61% objective response rate, with 24% achieving complete response and 37% achieving partial response.

The treatment showed promising safety, with limited toxicity observed; however, one patient experienced severe complications, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of temozolomide in patients with progressive low-grade glioma. Quinn, JA., Reardon, DA., Friedman, AH., et al.[2022]

In a study of 20 patients with various types of glioma, the combination of olaparib and temozolomide (TMZ) showed a 50% objective radiographic response rate in patients with recurrent IDH-mutant grade 2-3 gliomas, indicating potential efficacy for this specific group.

While the treatment was generally manageable, common side effects included fatigue and gastrointestinal issues, with 30% of patients requiring dose adjustments due to toxicity, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Olaparib and Temozolomide for the Treatment of Glioma: A Retrospective Case Series. Schaff, LR., Kushnirsky, M., Lin, AL., et al.[2023]

Temozolomide is primarily used for treating refractory central nervous system cancers like anaplastic astrocytoma and glioblastoma, but ongoing clinical trials are exploring its efficacy and safety in newly diagnosed gliomas and other types of tumors.

Research is also investigating different dosing schedules and combinations with other treatments, suggesting that temozolomide could be a versatile option in cancer therapy beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. Yung, WK.[2019]

The combination of Tumour Treating Fields (TTFields) with lomustine and temozolomide in patients with MGMT promoter methylated newly diagnosed glioblastoma showed a median progression-free survival of 20 months, indicating promising efficacy.

Safety analysis revealed that while some patients experienced significant adverse events, including hematologic and hepatotoxic effects, the treatment was generally well-tolerated with a high adherence rate of 83%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumour Treating Fields (TTFields) in combination with lomustine and temozolomide in patients with newly diagnosed glioblastoma. Lazaridis, L., Schäfer, N., Teuber-Hanselmann, S., et al.[2020]

In a phase II clinical trial involving 21 patients with newly diagnosed glioblastoma multiforme (GBM), the combination of temozolomide (TMZ) with radiotherapy resulted in a one-year survival rate of 58% and a median survival time of 15.7 months, indicating its efficacy in extending survival.

The treatment regimen was well-tolerated, with only mild to moderate non-hematological side effects and minimal severe hematological toxicity, suggesting that TMZ has a favorable safety profile compared to traditional chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. Lanzetta, G., Campanella, C., Rozzi, A., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4001735/

Phase 1/1b Study of Lonafarnib and Temozolomide in ... Efficacy analyses combined outcomes from patients enrolled on both the phase 1 and phase 1b components of the clinical trial. For overall efficacy combining ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4898271/

Lonafarnib (SCH66336) improves the activity of temozolomide ... In vivo, lonafarnib alone had a modest ability to inhibit orthotopic U87 tumors, radiation and temozolomide demonstrated better inhibition, while significant ...

3. ar.iiarjournals.org ar.iiarjournals.org/content/29/12/5171

Chemotherapy for Glioblastoma: Current Treatment and ... Overall survival was 27.2% at 2 years, 16.0% at 3 years, 12.1% at 4 years, and 9.8% (6.4-14.0) at 5 years in RT plus temozolomide group, versus 10.9%, 4.4%, 3.0 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00102648?term=AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(%22Glioma%22)%20AND%20AREA%5BInterventionSearch%5D(%22Temozolomide%22))&rank=9

Study Details | Lonafarnib and Temozolomide in Treating ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/cncr.28031

Phase 1/1b study of lonafarnib and temozolomide in patients ... The PFS-6 rate was 38% (95% confidence interval [CI] = 22%, 56%) and the median PFS was 3.9 months (95% CI = 2.5, 8.4). The median disease- ...

6. escholarship.org escholarship.org/content/qt4nb66879/qt4nb66879_noSplash_80cf3aeb5a772f198dcac82a4d622b0a.pdf

Molecularly targeted therapies for recurrent glioblastoma 60 In a Phase Ib clinical trial testing the efficacy of combination lonafarnib and temozolomide for recurrent glioblastoma, outcomes were relatively promising.