## Protocol Section
### Identification Module
**NCT ID:** NCT06428045

**Acronym:** STARLITE

**Brief Title:** STARLITE for Unresectable High-Grade Gliomas

**Official Title:** Synergistic Treatment With Antiretrovirals and Laser Interstitial Thermal thErapy (STARLITE) for Unresectable High-Grade Gliomas: A Phase 1 Study

#### Organization Study ID Info
**ID:** 20231163
#### Organization
**Class:** OTHER
**Full Name:** University of Miami
### Status Module
#### Completion Date
**Date:** 2029-05-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-20

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2028-05-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-08-31

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-20
**Study First Submit QC Date:** 2024-05-20
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Medtronic

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Miami

#### Responsible Party

**Investigator Affiliation:** University of Miami

**Investigator Full Name:** Ashish Shah

**Investigator Title:** Assistant Professor of Clinical

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** True

**Is FDA Regulated Drug:** True

**Is US Export:** False

**Oversight Has DMC:** True

### Description Module

**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 Module

**Conditions:**

- High Grade Glioma

**Keywords:**

- Unresectable High Grade Glioma

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** SEQUENTIAL

**Intervention Model Description:** Phase 1 dose escalation/de-escalation and dose expansion design.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 24

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

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

- Drug: Abacavir

- Drug: Lamivudine

- Drug: Ritonavir

- Drug: Temozolomide

- Radiation: Focal Radiotherapy

**Label:** Part 1: STARLITE Dose Escalation/De-Escalation Cohort

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 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.

**Intervention Names:**

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

- Drug: Abacavir

- Drug: Lamivudine

- Drug: Ritonavir

- Drug: Temozolomide

- Radiation: Focal Radiotherapy

**Label:** Part 2: STARLITE Dose Expansion Cohort

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Part 1: STARLITE Dose Escalation/De-Escalation Cohort

- Part 2: STARLITE Dose Expansion Cohort

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

**Name:** Magnetic Resonance (MR)-guided Laser Interstitial Thermal Therapy (LITT)

**Other Names:**

- MR-Guided LITT

**Type:** PROCEDURE

#### Intervention 2

**Arm Group Labels:**

- Part 1: STARLITE Dose Escalation/De-Escalation Cohort

- Part 2: STARLITE Dose Expansion Cohort

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

**Name:** Abacavir

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Part 1: STARLITE Dose Escalation/De-Escalation Cohort

- Part 2: STARLITE Dose Expansion Cohort

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

**Name:** Lamivudine

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- Part 1: STARLITE Dose Escalation/De-Escalation Cohort

- Part 2: STARLITE Dose Expansion Cohort

**Description:** 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 1 (starting dose): 300mg
* Dose Level 2: 450mg
* Dose Level 3: 600mg

**Name:** Ritonavir

**Other Names:**

- Norvir

- RTV

**Type:** DRUG

#### Intervention 5

**Arm Group Labels:**

- Part 1: STARLITE Dose Escalation/De-Escalation Cohort

- Part 2: STARLITE Dose Expansion Cohort

**Description:** 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 150-200 mg/m2 on days 1 through 5 of a four-week cycle for a total of six cycles of maintenance therapy.

**Name:** Temozolomide

**Other Names:**

- TMZ

**Type:** DRUG

#### Intervention 6

**Arm Group Labels:**

- Part 1: STARLITE Dose Escalation/De-Escalation Cohort

- Part 2: STARLITE Dose Expansion Cohort

**Description:** 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.

**Name:** Focal Radiotherapy

**Type:** RADIATION

### Outcomes Module

#### Primary Outcomes

**Description:** 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 6.0 (NCI CTCAE v6.0).

**Measure:** Number of Participants Experiencing Dose-Limiting Toxicity

**Time Frame:** Up to 28 days

**Description:** 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 6.0 (NCI CTCAE v6.0).

**Measure:** Number of Participants Experiencing Serious Adverse Events and Grade 3 or Higher Adverse Events

**Time Frame:** Up to 12 months

#### Secondary Outcomes

**Description:** PFS is defined as percentage of participants without disease progression at time of study discontinuation.

**Measure:** Progression-Free Survival (PFS)

**Time Frame:** Up to 24 months

**Description:** Overall Survival is defined as the percentage of participants who are still living at the time of study discontinuation.

**Measure:** Overall Survival (OS)

**Time Frame:** Up to 24 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Age ≥ 18 years.
2. 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).
3. Uni-focal or butterfly gliomas that can receive ≥70% of lesion volume ablated as determined by the treating surgeon.
4. 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.
5. Preoperative Karnofsky score ≥ 70 (APPENDIX A).
6. Patients must have demonstrable normal organ function as defined below within 14 days of surgery.

   1. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3
   2. Platelets ≥ 100,000 cells/mm3
   3. Hemoglobin ≥ 9.0 g/dL. Use of transfusion or other intervention to achieve this hemoglobin level is acceptable.
   4. 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.
   5. Electrocardiogram (ECG) without evidence of acute cardiac ischemia.
   6. Prothrombin time (PT)/International Normalized Ratio (INR) \<1.4
   7. Liver function tests: Aspartate aminotransferase (AST) and alanine transaminase (ALT) at or below 2.5 times the upper limit of normal (ULN).
   8. Sodium level \> 130 mg/L. Use of salt resection or hypertonic saline to achieve this sodium level is acceptable.
7. Patients must be able to understand and sign informed consent.

Exclusion Criteria:

1. Patients with human leukocyte antigen (HLA) HLA-B\*5701 hypersensitivity (Section 10.1.6.7).
2. Patients with sensitivity to abacavir, lamivudine, or ritonavir (Section 7.3.1).
3. Patients with a previous history of HIV infection.
4. Patients with uncontrolled hepatitis B or C infection.
5. 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.
6. Patients who have received chemotherapy or radiation for this disease.
7. Patients who are taking dofetilide (Section 4.10.1).
8. 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.
9. Patients not eligible to obtain MRI with and without contrast.
10. Recurrent HGG.
11. Presence of current infection, such as sepsis, meningitis, bacteremia, or pneumonia.
12. Fever within 48 hours of surgery (Temperature\> 38.0°C).
13. Severe co-morbidity that would confer excess risk of surgery, radiation, or chemotherapy, as determined by the treating physician.
14. Any co-morbidity or psychiatric ailment that in the Investigator's opinion will prevent administration or completion of protocol therapy.
15. Pregnant women.
16. Patients must be willing to use contraception as described in Section 4.11.
17. Patients receiving other investigational agents or concurrent enrollment in another therapeutic clinical trial.
18. Prisoners.
19. Adults unable to consent.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** ashah@med.miami.edu

**Name:** Ashish Shah, MD

**Phone:** (305) 243-6946

**Role:** CONTACT

**Contact 2:**

**Email:** MDelaFuente@med.miami.edu

**Name:** Macarena De La Fuente, MD

**Phone:** (305) 243-2858

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Miami

**Contacts:**

***Contact 1:***

- **Email:** ashah@med.miami.edu

- **Name:** Ashish Shah, MD

- **Phone:** 305-243-6946

- **Role:** CONTACT

***Contact 2:***

- **Email:** MDelaFuente@med.miami.edu

- **Name:** Macarena De La Fuente, MD

- **Phone:** (305) 243-2858

- **Role:** CONTACT

***Contact 3:***

- **Name:** Ashish Shah, MD

- **Role:** PRINCIPAL_INVESTIGATOR

***Contact 4:***

- **Name:** Macarena De La Fuente, MD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** University of Miami

**State:** Florida

**Zip:** 33136

#### Overall Officials

**Official 1:**

**Affiliation:** University of Miami

**Name:** Ashish Shah, MD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** University of Miami

**Name:** Macarena De La Fuente, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000018302

- Term: Neoplasms, Neuroepithelial

- ID: D000017599

- Term: Neuroectodermal Tumors

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009380

- Term: Neoplasms, Nerve Tissue

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M9020

- Name: Glioma

- Relevance: HIGH

- As Found: Glioma

- ID: M20446

- Name: Neoplasms, Neuroepithelial

- Relevance: LOW

- As Found: Unknown

- ID: M19845

- Name: Neuroectodermal Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M20388

- Name: Neuroectodermal Tumors, Primitive

- Relevance: LOW

- As Found: Unknown

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12325

- Name: Neoplasms, Nerve Tissue

- Relevance: LOW

- As Found: Unknown

- ID: T2519

- Name: Glioma

- Relevance: HIGH

- As Found: Glioma

- ID: T4092

- Name: Neuroepithelioma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000005910

- Term: Glioma

### Intervention Browse Module - Ancestors

- ID: D000017320

- Term: HIV Protease Inhibitors

- ID: D000084762

- Term: Viral Protease Inhibitors

- ID: D000011480

- Term: Protease Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000019380

- Term: Anti-HIV Agents

- ID: D000044966

- Term: Anti-Retroviral Agents

- ID: D000000998

- Term: Antiviral Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000065692

- Term: Cytochrome P-450 CYP3A Inhibitors

- ID: D000065607

- Term: Cytochrome P-450 Enzyme Inhibitors

- ID: D000018906

- Term: Antineoplastic Agents, Alkylating

- ID: D000000477

- Term: Alkylating Agents

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000018894

- Term: Reverse Transcriptase Inhibitors

- ID: D000019384

- Term: Nucleic Acid Synthesis Inhibitors

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: ANeo

- Name: Antineoplastic Agents

### Intervention Browse Module - Browse Leaves

- ID: M21394

- Name: Ritonavir

- Relevance: HIGH

- As Found: Additional

- ID: M21243

- Name: Lamivudine

- Relevance: HIGH

- As Found: Resistant

- ID: M350770

- Name: Abacavir

- Relevance: HIGH

- As Found: Exchange

- ID: M1692

- Name: Temozolomide

- Relevance: HIGH

- As Found: Head

- ID: M25428

- Name: Anti-Retroviral Agents

- Relevance: LOW

- As Found: Unknown

- ID: M19609

- Name: HIV Protease Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M14343

- Name: Protease Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M21350

- Name: Anti-HIV Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4314

- Name: Antiviral Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M30564

- Name: Cytochrome P-450 CYP3A Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M30537

- Name: Cytochrome P-450 Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M20942

- Name: Antineoplastic Agents, Alkylating

- Relevance: LOW

- As Found: Unknown

- ID: M3820

- Name: Alkylating Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20935

- Name: Reverse Transcriptase Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000019438

- Term: Ritonavir

- ID: D000019259

- Term: Lamivudine

- ID: C000106538

- Term: Abacavir

- ID: D000077204

- Term: Temozolomide

### Misc Info Module

- Version Holder: 2024-05-31
