STARLITE for Unresectable High-Grade Gliomas

NCT06428045 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 20231163
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

High Grade Glioma

Keywords

Unresectable High Grade Glioma

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing Dose-Limiting Toxicity

  The number of participants experiencing dose-limiting toxicity (DLT) during the first 28 days of antiretroviral therapy (ART) will be reported. Toxicity will be assessed by the treating physician and assigned severity and attribution using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0).

  Up to 28 days

• Number of Participants Experiencing Serious Adverse Events and Grade 3 or Higher Adverse Events

  The number of participants experiencing serious adverse events (SAEs) and Grade 3 or higher adverse events (AEs) will be reported. SAEs and AEs will be assessed by the treating physician and assigned severity and attribution using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0).

  Up to 12 months

Secondary Outcomes (2)

• Progression-Free Survival (PFS)

  Up to 24 months

• Overall Survival (OS)

  Up to 24 months

Study Arms (2)

Part 1: STARLITE Dose Escalation/De-Escalation Cohort

EXPERIMENTAL

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.

Procedure: Magnetic Resonance (MR)-guided Laser Interstitial Thermal Therapy (LITT); Drug: Abacavir; Drug: Lamivudine; Drug: Ritonavir; Drug: Temozolomide; Radiation: Focal Radiotherapy

Part 2: STARLITE Dose Expansion Cohort

EXPERIMENTAL

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.

Procedure: Magnetic Resonance (MR)-guided Laser Interstitial Thermal Therapy (LITT); Drug: Abacavir; Drug: Lamivudine; Drug: Ritonavir; Drug: Temozolomide; Radiation: Focal Radiotherapy

Interventions

Magnetic Resonance (MR)-guided Laser Interstitial Thermal Therapy (LITT) PROCEDURE

Participants will be administered MR-guided Laser Interstitial Thermal Therapy (LITT) as a single procedure, following stereotactic needle biopsy.

Also known as: MR-Guided LITT

Part 1: STARLITE Dose Escalation/De-Escalation Cohort; Part 2: STARLITE Dose Expansion Cohort

Abacavir DRUG

Participants will take one 600mg tablet of Abacavir orally once daily, as part of combination antiretroviral therapy (ART).

Part 1: STARLITE Dose Escalation/De-Escalation Cohort; Part 2: STARLITE Dose Expansion Cohort

Lamivudine DRUG

Participants will take one 300mg tablet of Lamivudine orally once daily, as part of combination antiretroviral therapy (ART)

Part 1: STARLITE Dose Escalation/De-Escalation Cohort; Part 2: STARLITE Dose Expansion Cohort

Ritonavir DRUG

Participants will take one tablet of Ritonavir (RTV) orally twice daily, as part of combination antiretroviral therapy (ART), at one of the following dose levels: * Dose Level 1: 100mg * Dose Level 2 (starting dose): 300mg * Dose Level 3: 400mg * Dose Level 4: 600mg

Also known as: Norvir, RTV

Part 1: STARLITE Dose Escalation/De-Escalation Cohort; Part 2: STARLITE Dose Expansion Cohort

Temozolomide DRUG

Participants will take Temozolomide (TMZ) via capsule orally, during and after focal radiotherapy, as part of standard of care adjuvant therapy. During focal radiotherapy, Temozolomide will be administered at a dose of 75 mg/m2 once daily for six weeks (42 days) on a continuous dosing regimen, including weekends and holidays. After completion of focal radiotherapy, Temozolomide will be administered at 150 mg/m\^2 on days 1 through 5 of Cycle 1, and at 200 mg/m\^2 on days 1 through 5 of Cycles 2 through 6, for a total of six 28-day cycles of maintenance therapy.

Also known as: TMZ

Part 1: STARLITE Dose Escalation/De-Escalation Cohort; Part 2: STARLITE Dose Expansion Cohort

Focal Radiotherapy RADIATION

Participants will be administered focal radiotherapy for six weeks (42 days), as part of adjuvant therapy, at a total dose of 50-60 grays (Gy) in 1.8-2.0 Gy fractions, depending on prognosis and as determined by the treating radiation oncologist.

Part 1: STARLITE Dose Escalation/De-Escalation Cohort; Part 2: STARLITE Dose Expansion Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Patients with a histologically confirmed or suspected high-grade glioma (HGG) by MRI.
• a. For cases with suspected HGG, intraoperative frozen section diagnoses of HGG must be made by pathologists (Section 4.4.1).
• Uni-focal or butterfly gliomas that can receive ≥70% of lesion volume ablated as determined by the treating surgeon.
• Gliomas must be located or positioned where surgical resection is either not feasible or high-risk as deemed by a group of surgical neuro-oncologists.
• Preoperative Karnofsky score ≥ 70 (APPENDIX A).
• Patients must have demonstrable normal organ function as defined below within 14 days of surgery.
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm3
• Platelets ≥ 100,000 cells/mm3
• Hemoglobin ≥ 9.0 g/dL. Use of transfusion or other intervention to achieve this hemoglobin level is acceptable.
• Blood urea nitrogen (BUN) ≤ 35 mg/dL and creatinine ≤ 1.9 mg/dL and estimated glomerular filtration rate (eGFR) or creatinine clearance rate \> 50 mL per minute.
• Electrocardiogram (ECG) without evidence of acute cardiac ischemia.
• Prothrombin time (PT)/International Normalized Ratio (INR) \<1.4
• Liver function tests: Aspartate aminotransferase (AST) and alanine transaminase (ALT) at or below 2.5 times the upper limit of normal (ULN).
• Sodium level \> 130 mg/L. Use of salt resection or hypertonic saline to achieve this sodium level is acceptable.

You may not qualify if:

• Patients with human leukocyte antigen (HLA) HLA-B\*5701 hypersensitivity (Section 10.1.6.7).
• Patients with sensitivity to abacavir, lamivudine, or ritonavir (Section 7.3.1).
• Patients with a previous history of HIV infection.
• Patients with uncontrolled hepatitis B or C infection.
• Patients who have received any surgical resection for this tumor.
• a. Patients who have received an open biopsy for this disease are still eligible for participation.
• Patients who have received chemotherapy or radiation for this disease.
• Patients who are taking dofetilide (Section 4.10.1).
• Patients on a regimen of 1 or more prohibited medications as described in Section 4.10.1 that cannot be discontinued or switched to a more compatible medication. For more information on prohibited and precautionary use medications for patients on this study, please see Section 4.10.
• Patients not eligible to obtain MRI with and without contrast.
• Recurrent HGG.
• Presence of current infection, such as sepsis, meningitis, bacteremia, or pneumonia.
• Fever within 48 hours of surgery (Temperature\> 38.0°C).
• Severe co-morbidity that would confer excess risk of surgery, radiation, or chemotherapy, as determined by the treating physician.
• Any co-morbidity or psychiatric ailment that in the Investigator's opinion will prevent administration or completion of protocol therapy.

Sponsors & Collaborators

• University of Miami: lead
• Medtronic: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Related Publications (1)

• Daftari M, Ramsoomair CK, Aaronson D, Seetharam D, Andreae EA, Wright L, Han S, Chandar J, Lu V, Govindarajan V, Ivan ME, Komotar RJ, de la Fuente M, Shah AH. Synergistic Treatment with Antiretrovirals and Laser Interstitial Thermal ThErapy (STARLITE) for unresectable glioblastoma: A phase 1 study protocol. PLoS One. 2025 Aug 28;20(8):e0328204. doi: 10.1371/journal.pone.0328204. eCollection 2025.

  PMID: 40875628 DERIVED

MeSH Terms

Conditions

Glioma

Interventions

Magnetic Resonance Spectroscopy; abacavir; Lamivudine; Ritonavir; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Dacarbazine; Triazenes; Imidazoles

Study Officials

• Ashish Shah, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

• Macarena De La Fuente, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ashish Shah, MD

CONTACT

(305) 243-6946; ashah@med.miami.edu

Macarena De La Fuente, MD

CONTACT

(305) 243-2858; MDelaFuente@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical

Model Details: Phase 1 dose escalation/de-escalation and dose expansion design.

Study Record Dates

• First Submitted: May 20, 2024
• First Posted: May 24, 2024
• Study Start: April 15, 2025
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2030
• Last Updated: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)