Liposomal Rhenium Re 186 in Treating Patients with Recurrent Glioblastoma
This phase I/II trial studies the side effects and best dose of liposomal rhenium Re 186 and to see how well it works in treating patients with glioblastoma that has come back (recurrent). Liposomal rhenium Re 186 consists of radioactive Re 186 placed inside of a nanoliposome. The nanoliposomes help carry radiation directly to tumor cells and not harm normal cells. The radioisotope releases radiation, which may directly kill tumor cells.
Inclusion Criteria
- At least 18 years of age
- Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator’s Institutional Review Board (IRB)/Ethics Committee
- For the Phase 1, histologically confirmed Grade III/IV recurrent Glioma (following 2021 World Health Organization [WHO] CNS5 glioma nomenclature, e.g., Astrocytoma, IDH-mutant grade 3 or 4; Glioblastoma, IDH-wildtype grade 4). For the Phase 2, histologically confirmed Glioblastoma (following 2021 WHO CNS5 nomenclature) * For the Phase 1, any number of recurrences may be included * For the Phase 2, limited to 1 recurrence
- Progression by RANO criteria or other clinically accepted neurooncology evaluation, following standard treatment options with known survival benefit (for any recurrence (e.g., surgery, temozolomide, radiation, and tumor treating fields [unless). Patient may be included in study if medically unable or unwilling]) to follow standard treatment options for any recurrence
- Patients who receive treatment with antiepileptic medications must have a two week history of stable dose of antiepileptic without seizures prior to study start (dosing)
- 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 prior to study start (dosing)
- A volume of enhancing tumor which falls within the treatment field volume being evaluated in the respective phase/cohort. For Phase 2 only, tumor sizes are limited to =< (less than or equal to) 20 cm^3
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2; Karnofsky Performance Status >= 60
- Life expectancy of at least 2 months
- Bilirubin =< 1.5 times upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 times upper limit of normal (ULN)
- Serum creatinine =< 1.5 x ULN
- Absolute neutrophil count (ANC) >= 1000 cells/uL (without hematologic support)
- Platelet count >= 100,000/uL (without hematologic support)
- Hemoglobin >= 9.0 g/dL (without hematologic support)
- 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 (for example, surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an intrauterine device [IUD]) with their partner from entry into the study through 6 months after the last dose
- PART 2: Bevacizumab naive glioblastoma with no more than 1 recurrence
Exclusion Criteria
- The subject has evidence of acute intracranial or intratumoral hemorrhage either by magnetic resonance imaging (MRI) or computerized tomography (CT) scan; subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible
- The subject is unable or contraindicated to undergo MRI scan (e.g., has pacemaker or medically unstable)
- The subject has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade =< 1 from AEs (except alopecia, anemia, and lymphopenia) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study
- The subject is pregnant or breast-feeding
- 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 * Active medically significant infection unresponsive to antibiotics (e.g., non-healing wound, ulcer), uncontrolled systemic infection, or bone fracture * Clinically significant cardiac arrhythmias not controlled by appropriate medications * Untreated hypothyroidism * Symptomatic congestive heart failure or unstable angina pectoris within 3 months of study start (dosing) * Myocardial infarction, stroke, or transient ischemic attack within 6 months of study start (dosing) * Known active malignancy (other than glioma) except non-melanoma skin cancer or carcinoma in-situ in the cervix unless primary investigator (PI) determines it would not impact patient safety or efficacy determinations
- The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding
- The subject has received any of the following prior anticancer therapy: * Prior treatment with bevacizumab * 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 or non-cytotoxic hormonal therapy (e.g., tamoxifen) within 14 days or 5 half-lives, whichever is shorter, of study start (dosing) * Biologic agents (antibodies, immune modulators, vaccines, and cytokines) within 21 days prior of study start (dosing) * Nitrosoureas or mitomycin C within 42 days of study start (dosing) * Metronomic/protracted low-dose chemotherapy within 14 days of study start (dosing) * Other cytotoxic chemotherapy within 28 days of study start (dosing) * Prior treatment with carmustine wafers * Investigational agents within 28 days of study start (dosing)
- Multifocal progression or involvement of the leptomeninges
- Psychiatric illness/social situations that would limit compliance with the study requirements
- Infratentorial disease
- The subject has a tumor located within 1-2 cm of a ventricle AND it is determined by the surgeon, PI, and sponsor to be a risk for drug extravasation to the subarachnoid space if given catheter placement and drug administration
Additional locations may be listed on ClinicalTrials.gov for NCT01906385.
Locations matching your search criteria
United States
Texas
Dallas
Houston
San Antonio
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose of liposomal rhenium Re 186 (186RNL) by convection enhanced delivery (CED) at the time of planned stereotactic biopsy when necessary as standard of care. (Phase 1)
II. To assess overall survival (OS) following 186RNL administration by convection enhanced delivery (CED) in patients with recurrent glioblastoma. (Phase 2)
SECONDARY OBJECTIVES:
I. To assess the safety of single dose 186RNL by CED. (Phase 1)
II. To assess the dose distribution of 186RNL by CED. (Phase 1)
III. To determine the overall response rate by Radiographic Assessment in Neuro-Oncology (RANO) criteria following 186RNL treatment. (Phase 1)
IV. To determine disease specific progression-free survival after 186RNL treatment. (Phase 1)
V. To assess the safety and tolerability of 186RNL by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0 criteria. (Phase 2)
VI. To determine the objective response rate (ORR) from the date of complete or partial response or Serious Treatment-Emergent Adverse Events (Safety and Tolerability) up to 3 years. (Phase 2)
VII. To determine progression free survival at 6 months (PFS-6) as measured from the initiation of study treatment until the date of first documented progression by modified Response Assessment in Neuro-Oncology Criteria (RANO) criteria (recognizing the potential of pseudo progression significantly complicating the use of the RANO criteria) or date of death from any cause up to 6 months. (Phase 2)
VIII. To determine progression free survival (PFS) as measured from the initiation of study treatment until the date of first documented progression by modified RANO criteria (recognizing the potential of pseudo progression significantly complicating the use of the RANO criteria) where progression is defined as >25% in the sum of products of the perpendicular diameters of CE lesions, evidence of new lesion(s), or date of death from any cause, whichever comes first, up to 3 years. (Phase 2)
IX. Evaluate assessing quality of life using a Quality-of-Life Questionnaire (developed in collaboration with established glioblastoma patient advocacy groups). (Phase 2)
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive liposomal rhenium Re 186 via convection enhanced delivery on day 1 after surgery on study. Additionally, patients undergo standard of care tumor catheterization and stereotactic biopsy, blood collection, single photon emission computed tomography (SPECT)/computed tomography (CT), and planar imaging on study. Patients also undergo magnetic resonance imaging (MRI) during screening and throughout the study.
After completion of study treatment, patients are followed up every 3 months for 3 years.
Trial PhasePhase I/II
Trial Typetreatment
Lead OrganizationCancer Therapy and Research Center at The UT Health Science Center at San Antonio
Principal InvestigatorAndrew Jacob Brenner
- Primary IDCTRC# 12-02
- Secondary IDsNCI-2014-00900, NCI-2014-00412, 1149367, 1-874640-1, 193831, 20141749, CTRC 12-02, HSC20140450X
- ClinicalTrials.gov IDNCT01906385