STARLITE for Unresectable Brain Tumors

(STARLITE Trial)

Overseen By Macarena De La Fuente, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Miami

Must not be taking: Dofetilide, Abacavir, Lamivudine, Ritonavir

Disqualifiers: HIV, Hepatitis B/C, Recurrent HGG, others

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

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests treatments for individuals with newly diagnosed high-grade brain tumors that cannot be surgically removed. Researchers aim to observe how tumors respond to a combination of therapies, including MR-guided Laser Interstitial Thermal Therapy (LITT, a type of laser therapy) and medications such as Abacavir, Lamivudine, Ritonavir, and Temozolomide. The trial also seeks to identify any side effects of the treatment. It is suitable for those with a single or butterfly-shaped glioma (a type of brain tumor) that cannot be surgically removed. Participants should be able to undergo MRI scans and have normal organ function. 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 innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that patients on certain prohibited medications must discontinue or switch to a more compatible medication. Please consult with the trial team for specific guidance on your medications.

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

A previous study found that the combination of Abacavir, Lamivudine, and Ritonavir was generally safe, with no major harmful effects reported. These drugs are usually well-tolerated when taken together.

Research has shown that MR-guided Laser Interstitial Thermal Therapy (LITT) is a good option for treating brain tumors like glioblastoma. It has been safely used in patients with both new and recurring brain tumors.

Temozolomide, often used with radiation therapy, has proven beneficial in treating glioblastoma. It can improve survival rates without causing severe side effects.

Overall, past research indicates that the treatments under study have been well-tolerated, with manageable side effects. However, this trial is in an early stage, and the main goal is to understand the safety of these treatments for people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the STARLITE treatments for unresectable brain tumors because they combine advanced laser technology with innovative drug therapies. Unlike the traditional approach, which mainly involves surgery, radiation, and chemotherapy, this treatment uses MR-guided Laser Interstitial Thermal Therapy (LITT) to precisely target and heat tumor tissue, potentially reducing damage to surrounding areas. Additionally, the combination of antiretroviral drugs like Abacavir and Lamivudine with Ritonavir could offer a new way to enhance treatment effectiveness. This blend of cutting-edge laser precision and novel drug combinations aims to improve outcomes for patients with challenging brain tumors.

What evidence suggests that this trial's treatments could be effective for unresectable brain tumors?

Research shows that MR-guided Laser Interstitial Thermal Therapy (LITT), which participants in this trial will undergo, is a promising treatment for brain tumors. Studies have found it safe and effective, especially for tumors difficult to remove surgically. LITT precisely targets the tumor and allows for quick recovery.

In this trial, researchers are also investigating antiretroviral drugs, including Abacavir, Lamivudine, and Ritonavir, for potential benefits beyond treating viral infections. Some studies suggest these drugs might have anticancer effects and could complement other treatments, although more research is needed for glioblastoma.

Temozolomide, part of the adjuvant therapy participants will receive, is a well-known chemotherapy drug. It has been shown to help brain cancer patients live longer when used with radiation. In some studies, it increased the chance of surviving two years from 10% to about 26.5%, making it an important part of the treatment plan for aggressive brain tumors. ^{1 6 7 8 9}

Who Is on the Research Team?

Ashish B. Shah, M.D.

Principal Investigator

University of Miami

Macarena I. De La Fuente

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for individuals with newly diagnosed high-grade gliomas (a type of brain tumor) that cannot be surgically removed. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may have restrictions based on other medical treatments or conditions.

Inclusion Criteria

My brain tumor is in a place where surgery is too risky or not possible.

My MRI suggests I have a high-grade brain tumor.

My brain tumor can be mostly removed by surgery, as determined by my surgeon.

Exclusion Criteria

Patients receiving other investigational agents or concurrent enrollment in another therapeutic clinical trial

Prisoners

I am allergic to the HLA-B*5701 protein.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants undergo MR-guided LITT after biopsy and begin combination antiretroviral therapy (ART) with Abacavir, Lamivudine, and Ritonavir

4 weeks

Multiple visits for monitoring and treatment initiation

Adjuvant Therapy

Participants receive focal radiotherapy for six weeks and Temozolomide therapy up to Day 180

24 weeks

Regular visits for radiotherapy and chemotherapy administration

Extended Treatment

Participants continue ART for up to 12 months

12 months

Monthly visits for ART monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Abacavir
• Lamivudine
• MR-guided Laser Interstitial Thermal Therapy (LITT)
• Ritonavir
• Temozolomide

Trial Overview The STARLITE trial tests a combination of therapies: MR-guided Laser Interstitial Thermal Therapy (LITT), antiviral drugs Abacavir, Lamivudine, Ritonavir, Focal Radiotherapy, and the chemotherapy drug Temozolomide to see how they affect inoperable high-grade gliomas.

How Is the Trial Designed?

Group I: Part 2: STARLITE Dose Expansion Cohort Experimental Treatment 6 Interventions

Participants in this group will undergo Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MR-guided LITT) after biopsy on Day 0. On Day 7, participants will begin combination antiretroviral therapy (ART) consisting of Abacavir, Lamivudine, and the recommended phase 2 dose (RP2D) of Ritonavir determined in Part 1. Participants will receive up to 12 months of ART. Beginning Day 14 through Day 180, participants will receive adjuvant therapy, standard of care consisting of focal radiotherapy and Temozolomide therapy. Participants will receive focal radiotherapy for six weeks (42 days), and Temozolomide therapy, during and following radiotherapy up to Day 180. Participants will receive up to 12 months of study therapy, followed by up to 12 months of follow-up. Total participation duration is up to 24 months. Total participation is approximately two years.

Group II: Part 1: STARLITE Dose Escalation/De-Escalation Cohort Experimental Treatment 6 Interventions

Participants in this group will undergo Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MR-guided LITT) on Day 0 after stereotactic needle biopsy. On Day 7, participants will begin combination antiretroviral therapy (ART) consisting of Abacavir, Lamivudine, and dose escalation/de-escalation of Ritonavir (RTV), to determine the recommended Phase 2 dose (RP2D) of Ritonavir. Participants will receive up to 12 months of ART. Beginning Day 14 through Day 180, participants will receive adjuvant therapy, standard of care consisting of focal radiotherapy and Temozolomide therapy. Participants will receive focal radiotherapy for six weeks (42 days). Participants will be administered Temozolomide up to Day 180. Participants will receive up to 12 months of study therapy, followed by up to 12 months of follow-up. Total participation duration is up to 24 months.

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Medtronic

Industry Sponsor

Trials

627

Recruited

767,000+

Geoff Martha

Medtronic

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Richard Kuntz

Medtronic

Chief Medical Officer since 2023

MD, MSc

Published Research Related to This Trial

In a study of 103 glioblastoma patients treated with standard temozolomide and radiotherapy, the median overall survival was found to be 13.7 months, highlighting the effectiveness of this treatment regimen.

Three key prognostic factors were identified that negatively impacted overall survival: age over 65 years, a Medical Research Council (MRC) scale score of 3-4, and the occurrence of postoperative complications, suggesting that these factors can help predict patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy. Verlut, C., Mouillet, G., Magnin, E., et al.[2020]

Temozolomide is a chemotherapeutic agent that effectively crosses the blood-brain barrier and has shown a good safety profile in treating brain metastases from solid tumors, with clinical activity observed in heavily pretreated patients.

In a randomized phase II trial, temozolomide combined with radiation therapy resulted in a significantly higher objective response rate (96% vs. 67%) compared to radiation alone, particularly benefiting patients with newly diagnosed brain and lung metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide for treating brain metastases. Abrey, LE., Christodoulou, C.[2019]

Temozolomide (TMZ) is the only anticancer drug proven to improve survival in glioblastoma when used with radiotherapy, showing high concentrations in brain tumors and cerebrospinal fluid, which enhances its effectiveness.

Molecular markers like MGMT promoter methylation can predict better responses to TMZ treatment, but side effects such as myelosuppression and nausea are common, necessitating precautions like prophylaxis against Pneumocystis carinii pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Temozolomide: Temodal]. Shinoura, N., Yamada, R., Tabei, Y., et al.[2018]

Temozolomide (TMZ) is an effective oral treatment for recurrent glioblastoma multiforme, showing nearly 100% bioavailability and a favorable safety profile, making it a promising option for patients with this aggressive brain cancer.

Research is ongoing to enhance the efficacy of TMZ by combining it with other treatments like chemotherapy, radiation, and immunotherapy, as well as exploring alternative dosing strategies to overcome resistance in gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions in the treatment of malignant gliomas with temozolomide. Prados, MD.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12393708/

Synergistic Treatment with Antiretrovirals and Laser Interstitial ... The ART regimen will consist of abacavir, lamivudine, and ritonavir. The abacavir+lamivudine tablets will be taken orally once daily at a ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11083594/

Antiretroviral Drug Repositioning for Glioblastoma - PMC The use of antiretroviral therapy has shown promising antineoplastic effects in multiple cancers; however, its efficacy in glioblastoma is ...

3. researchgate.net researchgate.net/publication/346269298_Drug_repositioning_of_antiretroviral_ritonavir_for_combinatorial_therapy_in_glioblastoma

Drug repositioning of antiretroviral ritonavir for ... An ART regimen of abacavir, lamivudine, and ritonavir will be administered followed by SoC adjuvant therapy in patients with newly-diagnosed, unresectable ...

4. researchgate.net researchgate.net/publication/380223554_Antiretroviral_Drug_Repositioning_for_Glioblastoma

(PDF) Antiretroviral Drug Repositioning for Glioblastoma An ART regimen of abacavir, lamivudine, and ritonavir will be administered followed by SoC adjuvant therapy in patients with newly-diagnosed ...

5. scholarship.miami.edu scholarship.miami.edu/esploro/search/outputs?query=creator,exact,Komotar%20Ricardo%20J&page=1&sort=date_d&institution=01UOML_INST

1–10 of 874 results - Scholarship@Miami An ART regimen of abacavir, lamivudine, and ritonavir will be administered followed by SoC adjuvant therapy in patients with newly-diagnosed, unresectable ...

6. mdpi.com mdpi.com/2072-6694/16/9/1754

Antiretroviral Drug Repositioning for Glioblastoma Outcomes for glioblastoma (GBM) remain poor despite standard-of-care treatments including surgical resection, radiation, and chemotherapy.

7. researchgate.net researchgate.net/publication/395021590_Synergistic_Treatment_with_Antiretrovirals_and_Laser_Interstitial_Thermal_ThErapy_STARLITE_for_unresectable_glioblastoma_A_phase_1_study_protocol

(PDF) Synergistic Treatment with Antiretrovirals and Laser ... An ART regimen of abacavir, lamivudine, and ritonavir will be administered followed by SoC adjuvant therapy in patients with newly-diagnosed, ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01332929

Safety Evaluation of a Combination of Brain Radiation ... Despite the treatment, the patient outcome is poor and brain metastasis become a major cause of death from cancer. Some recent studies showed an increase ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23195671/

Abacavir/lamivudine fixed-dose combination with ritonavir ... The new combination of ABC/3TC/DRV/r demonstrates a high rate of antiviral activity with no major toxicity. The drug combination appears to be generally safe ...