Maximum Tolerated Dose, Safety, and Efficacy of Rhenium Nanoliposomes in Recurrent Glioma (ReSPECT)

• Status: Recruiting
• Trial end date: 2025-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a multi-center, sequential cohort, open-label, volume and dose escalation study of the safety, tolerability, and distribution of 186RNL given by convection enhanced delivery to patients with recurrent or progressive malignant glioma after standard surgical, radiation, and/or chemotherapy treatment. The study uses a modified Fibonacci dose escalation, followed by an expansion at the maximum tolerated dose (MTD) to determine efficacy. The starting absorbed dose is 1mCi in a volume of 0.660mL.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Plus Therapeutics
• Collaborator: National Cancer Institute (NCI)

Criteria

Inclusion Criteria:

1. At least 18 years of age

2. Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee

3. Histologically confirmed glioma

4. Progression by RANO criteria following standard treatment options with known survival benefit (Temozolomide, Radiation, and Tumor Treating Fields [unless unwilling])

5. Patients who receive treatment with antiepileptic medications must have a two week history of stable dose of antiepileptic without seizures prior to dosing

6. Patients with corticosteroid requirements to control cerebral edema must be maintained at a stable or decreasing dose for a minimum of two weeks without progression of clinical symptoms

7. A volume of enhancing tumor which falls within the treatment field volume being evaluated in the respective cohort (see 4.1 Design)

8. ECOG performance status of 0 to 2

9. Life expectancy of at least 2 months

10. Acceptable liver function:

• Bilirubin ≤ 1.5 times upper limit of normal

• AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal (ULN);

11. Acceptable renal function:

• Serum creatinine ≤1.5xULN

12. Acceptable hematologic status (without hematologic support):

• ANC ≥1000 cells/uL

• Platelet count ≥100,000/uL

• Hemoglobin ≥9.0 g/dL

13. All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose

For part 2:

14. Bevacizumab naïve glioblastoma with no more than 1 recurrence

Exclusion Criteria:

1. The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible.

2. The subject is unable to undergo MRI scan (eg, has pacemaker).

3. The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered prior to study.

4. The subject is pregnant or breast-feeding.

5. The subject has serious intercurrent illness, as determined by the treating physician, that would compromise either patient safety or study outcomes such as:

• hypertension (two or more blood pressure readings performed at screening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment

• Non-healing wound, ulcer, or bone fracture

• Clinically significant cardiac arrhythmias

• Untreated hypothyroidism

• Uncontrolled systemic infection

• Symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug

• Myocardial infarction, stroke, transient ischemic attack within 6 months

• Known active malignancy (other than glioma) except non-melanoma skin cancer or carcinoma in-situ in the cervix

6. The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding

7. The subject has received any of the following prior anticancer therapy:

• Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy, or intra-operative radiotherapy (IORT) to the target site.

• Radiation therapy within 12 weeks of screening

• Systemic therapy (including investigational agents and small-molecule kinase inhibitors) or non-cytotoxic hormonal therapy (eg, tamoxifen) within 14 days or 5 half-lives, whichever is shorter, prior first dose of study drug

• Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug

• Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug

• Prior treatment with carmustine wafers

• Patients who are currently receiving any other investigational agents and/or who have received an investigational agent in the prior 28 days

8. Multifocal progression or involvement of the leptomeninges

9. Psychiatric illness/social situations that would limit compliance with the study requirements

10. Infratentorial disease