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

34 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Lonafarnib and Temozolomide for treating glioblastoma?

Temozolomide is a well-established chemotherapy drug for treating glioblastoma, showing effectiveness in both newly diagnosed and recurrent cases. Lonafarnib, although primarily studied in preclinical models, has shown potential activity against glioma, suggesting that the combination with Temozolomide could be promising for glioblastoma treatment. ^{1 2 3 4 5}

Is the combination of Lonafarnib and Temozolomide safe for humans?

Temozolomide, used in combination with other treatments, has shown common side effects like fatigue, gastrointestinal symptoms, and blood-related issues, with some patients needing dose adjustments or stopping treatment due to these effects. Lonafarnib, when studied with Temozolomide for glioblastoma, is part of ongoing research to understand its safety profile. ^{1 2 3 4 5}

How is the drug combination of Lonafarnib and Temozolomide unique for treating glioblastoma?

The combination of Lonafarnib and Temozolomide is unique because Lonafarnib is a farnesyltransferase inhibitor, which has shown activity in preclinical glioma models, and Temozolomide is an established first-line chemotherapy for glioblastoma. This combination targets the cancer cells in a novel way compared to standard treatments. ^{1 3 5 6 7}

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of lonafarnib when given together with temozolomide and to see how well they work in treating patients with glioblastoma multiforme that is has come back or did not respond to previous treatment with temozolomide. Lonafarnib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving lonafarnib together with temozolomide may kill more tumor cells.

Research Team

Vinay Puduvalli, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase 1/1b study of lonafarnib and temozolomide in patients with recurrent or temozolomide refractory glioblastoma. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of temozolomide in patients with progressive low-grade glioma. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Combination Olaparib and Temozolomide for the Treatment of Glioma: A Retrospective Case Series. [2023]

5. Greece pubmed.ncbi.nlm.nih.gov

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. [2018]

6. Greece pubmed.ncbi.nlm.nih.gov

Sunitinib Malate plus Lomustine for Patients with Temozolomide-refractory Recurrent Anaplastic or Low-grade Glioma. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

Tumour Treating Fields (TTFields) in combination with lomustine and temozolomide in patients with newly diagnosed glioblastoma. [2020]