STARLITE for Unresectable High-Grade Gliomas

University of Miami

Status and phase: Enrolling; Phase 1

Conditions: High Grade Glioma

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06428045

20231163

Details and patient eligibility

About

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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

24 participants in 2 patient groups

Part 1: STARLITE Dose Escalation/De-Escalation Cohort

Experimental group

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.

Treatment:

Drug: Ritonavir

Drug: Lamivudine

Drug: Abacavir

Drug: Temozolomide

Radiation: Focal Radiotherapy

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

Part 2: STARLITE Dose Expansion Cohort

Experimental group

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.

Treatment:

Drug: Ritonavir

Drug: Lamivudine

Drug: Abacavir

Drug: Temozolomide

Radiation: Focal Radiotherapy

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