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

NCT01906385 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: CTRC 12-0214-450X201417491R01CA235800-01A1
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Glioma

Keywords

Glioma; Brain Tumor; Radiotherapy; Glioblastoma; Recurrent Glioblastoma; Rhenium; Rhenium Nanoliposome; Brain Cancer; GBM; High Grade Glioma; Glioblastoma Multiform; Grade IV Astrocytoma

Outcome Measures

Primary Outcomes (2)

• Phase 1: Maximum Tolerated Dose

  Evaluation of any toxicity associated with research treatment per Common Toxicity Criteria for Adverse Events.

  90 days

• Phase 2: Overall Survival

  To assess overall survival (OS) following 186RNL administration by convection enhanced delivery (CED) in patients with recurrent glioma.

  12 Months

Secondary Outcomes (9)

• Phase 1: Dose Distribution

  Up to 7 days

• Phase 1: Response rate

  8 weeks followed by standard of care

• Phase 1: Survival

  6 months

• Phase 1: Safety of single dose of treatment

  Up to 3 years

• Phase 2: Safety and tolerability of 186RNL

  Up to 3 years

Study Arms (1)

186Rhenium Liposome Treatment

EXPERIMENTAL

Arm Phase I: Experimental: Dose Escalation for Cohorts 1-8 Each participant will receive a single administration of 186RNL. At each dose level, a minimum of three to a maximum of six participants will be enrolled. If no dose limiting toxicity is observed in the initial three participants, then the next higher dose level cohort will open for enrollment. The dose escalation scheme will follow a modified Fibonacci dose escalation scheme as shown below: COHORT ACTIVITY Cohort 1 (1.0 mCi) Cohort 2 (2.0 mCi) Cohort 3 (4.0 mCi) Cohort 4 (8.0 mCi) Cohort 5 (13.4 mCi) Cohort 6 (22.3 mCi) Cohort 7 (31.2 mCi) Cohort 8 (41.5 mCi) Phase 2: Single arm, prospective study utilizing a non-DLT dose obtained from the dose escalation portion of IND 116117, NIH-NCI Grant (22.3 mCi (total 186RNL activity) at a concentration of 2.5 mCi/mL and 8.8 mL total volume).

Drug: Rhenium Liposome Treatment

Interventions

Rhenium Liposome Treatment DRUG

At the time of stereotactic biopsy a catheter will be placed within the tumor using stereotactic guidance. Once the patient has adequately recovered from the procedure as determined by the neurosurgeon, 186RNL will be infused through the CED catheter at the predetermined dose. Spectroscopic imaging will then be obtained at predefined time points to visualize the distribution of the 186RNL as well as calculated the actual dose retained within the tumor. Patients will be monitored longitudinally for evidence of toxicity and response by MRI.

Also known as: Rhenium-186 NanoLiposome

186Rhenium Liposome Treatment

Eligibility Criteria

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

You may qualify if:

• 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 IRB/Ethics Committee.
• Histologically confirmed Grade III/IV recurrent Glioma (following 2021 WHO CNS5 glioma nomenclature, e.g., Astrocytoma, IDH-mutant grade 3 or 4; Glioblastoma, IDH-wildtype grade 4).
• 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). 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).
• Patients with Grade III/IV Glioma (following 2021 WHO CNS5 glioma nomenclature, e.g., Astrocytoma, IDH-mutant grade 3 or 4; Glioblastoma, IDH-wildtype grade 4) which falls within the treatment field volume.
• ECOG performance status of 0 to 2; Karnofsky Performance Status ≥ 60.
• Life expectancy of at least 2 months.
• Acceptable liver function:
• Bilirubin ≤ 1.5 times upper limit of normal
• AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal (ULN)
• Acceptable renal function:
• a. Serum creatinine ≤1.5xULN
• Acceptable hematologic status (without hematologic support):

You may not qualify if:

• 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 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, which 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 prior to study drug
• myocardial infarction, stroke, or transient ischemic attack within 6 months prior to study drug
• known active malignancy (other than glioma) except non-melanoma skin cancer or carcinoma in-situ in the cervix unless 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

Sponsors & Collaborators

• Plus Therapeutics: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Northshore University Hospital

Manhasset, New York, 11030, United States

RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

The Cancer Therapy and Research Center at UTHSCSA

San Antonio, Texas, 78229, United States

RECRUITING

Related Publications (1)

• Wu C, Hormuth DA 2nd, Christenson CD, Woodall RT, Abdelmalik MRA, Phillips WT, Hughes TJR, Brenner AJ, Yankeelov TE. Image-guided patient-specific optimization of catheter placement for convection-enhanced nanoparticle delivery in recurrent glioblastoma. Comput Biol Med. 2024 Sep;179:108889. doi: 10.1016/j.compbiomed.2024.108889. Epub 2024 Jul 19.

  PMID: 39032243 DERIVED

MeSH Terms

Conditions

Glioma; Brain Neoplasms; Glioblastoma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Astrocytoma

Study Officials

• Andrew J Brenner, PhD

  The Cancer Therapy and Research Center at UTHSCSA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachael Hershey

CONTACT

1(210) 791-8723; patients@respect-trials.com

Andrew Brenner, PhD

CONTACT

1(210) 791-8723; patients@respect-trials.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1: • Single arm, prospective study utilizing a modified Fibonacci dose escalation scheme. Phase 2: • Single arm, prospective study utilizing a non-DLT dose obtained from the dose escalation portion of IND 116117, NIH-NCI Grant (22.3 mCi (total 186RNL activity) at a concentration of 2.5 mCi/mL and 8.8 mL total volume).

Study Record Dates

• First Submitted: January 11, 2012
• First Posted: July 24, 2013
• Study Start: June 3, 2015
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 26, 2025

Record last verified: 2025-03

Locations

US (3)