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

Trial Summary

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.

What safety data exists for the treatment options in the STARLITE trial for unreseactable brain tumors?

Abacavir and lamivudine, used in HIV treatment, have been associated with some adverse effects. Abacavir can cause serious allergic reactions and may have cardiovascular effects, while lamivudine is generally well-tolerated. These drugs have been studied for safety in HIV patients, but not specifically for brain tumors. ^{1 2 3 4 5}

How is the STARLITE treatment for unresectable brain tumors different from other treatments?

The STARLITE treatment is unique because it combines multiple drugs, including Abacavir, Lamivudine, Ritonavir, and Temozolomide, with MR-guided Laser Interstitial Thermal Therapy (LITT), which is a novel approach for targeting brain tumors. This combination aims to enhance the effectiveness of Temozolomide, which is known to cross the blood-brain barrier and has shown activity against brain tumors, while also addressing drug resistance issues. ^{6 7 8 9 10}

What is the purpose of this trial?

The purpose of this study is to determine whether newly diagnosed high-grade glioma(s) that cannot be removed surgically change as a result of the study treatment; and to identify and evaluate the potential side effects (good and bad) of the study treatment in patients with newly diagnosed high-grade glioma(s) that cannot be removed surgically.

Research Team

Ashish B. Shah, M.D.

Principal Investigator

University of Miami

Macarena I. De La Fuente

Principal Investigator

University of Miami

Eligibility Criteria

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

Prisoners

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

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

Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. [2022]

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

Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study. [2022]

3. France pubmed.ncbi.nlm.nih.gov

Zidovudine, tenofovir or abacavir? Different adverse effect profiles. [2019]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness Analysis of Kivexa® (lamivudine/abacavir sulfate) in Human Immunodeficiency Virus Infected Korean Patients. [2020]

5. England pubmed.ncbi.nlm.nih.gov

A prospective, 96-week study of the impact of Trizivir, Combivir/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral-naive patients: effect of sex and ethnicity. [2022]

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

miR-1268a regulates ABCC1 expression to mediate temozolomide resistance in glioblastoma. [2019]

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

Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy. [2020]

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

Temozolomide for treating brain metastases. [2019]

9. Japan pubmed.ncbi.nlm.nih.gov

[Temozolomide: Temodal]. [2018]

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

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