Intraventricular Administration of Rhenium-186 NanoLiposome for Leptomeningeal Metastases (ReSPECT-LM)

• ClinicalTrials.gov Identifier: NCT05034497
• Recruitment Status: Recruiting
• First Posted: September 5, 2021
• Last Update Posted: December 8, 2022
• Sponsor: Plus Therapeutics
• Information provided by (Responsible Party): Plus Therapeutics

Study Description

Brief Summary:

This is an open-label Phase I clinical study that will administer a single dose of 186RNL via intraventricular catheter for treatment of Leptomeningeal Metastases (LM).

Condition or disease	Intervention/treatment	Phase
Leptomeningeal Metastasis	Drug: 186RNL	Phase 1

Detailed Description:

This Phase I clinical study evaluates a single dose of 186RNL (radionuclide clinical study drug) administered through an intraventricular catheter (Ommaya reservoir) in participants with Leptomeningeal Metastases (LM).

The clinical study treatment consists of a single administered 5cc dose of 186RNL per participant.

The clinical study will include the evaluation of three separate dose levels. Three to six participants may be treated at each dose.

The maximum number of participants to be enrolled in the study is 18.

The clinical study treatment will be administered, following a CSF flow study, on an outpatient basis by the clinical study physician.

Participants will be followed for up to 12 months after the clinical study drug is administered.

The U.S. Food and Drug Administration (FDA) has not approved 186RNL for this specific disease.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Phase 1 Clinical Study to Determine the Maximum Tolerated Dose/Maximum Feasible Dose, Safety,& Efficacy of Single Dose Rhenium-186 NanoLiposome (186RNL) Administered Via Intraventricular Catheter for Leptomeningeal Metastases
• Actual Study Start Date: December 6, 2021
• Estimated Primary Completion Date: July 30, 2023
• Estimated Study Completion Date: December 30, 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: Dose Escalation for Cohorts 1-3; Each participant will receive a single 5cc 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 (6.6 mCi) Cohort 2 (13.2 mCi) Cohort 3 (26.4 mCi)

Drug: 186RNL; All participants will be required to have an Ommaya Reservoir and a CSF Flow Study. Participants will receive a single 5cc dose of 186RNL via Ommaya Reservoir.; Other Name: Rhenium-186 NanoLiposome

Outcome Measures

Primary Outcome Measures :

1. Incidence and severity of adverse events (AE) and serious adverse events (SAE) [ Time Frame: 12 months ]
   Safety will be evaluated by the incidence of AEs and SAEs graded according CTCAE version 5.0.
2. Incidence of dose-limiting toxicities (DLT) [ Time Frame: 12 months ]
   Maximum Tolerated Dose (MTD) will be evaluated by testing increasing doses for cohorts 1 to 3 with 3 to 6 participants in each cohort. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in > 33% of participants.

Secondary Outcome Measures :

1. Determination of the overall response rate (ORR) [ Time Frame: 12 months ]
   Determine the overall response rate (ORR) defined as the proportion of all evaluable participants achieving a response as the best overall response at the time of progression.
2. Determination of the duration of response (DoR) [ Time Frame: 12 months ]
   Determine the duration of response (DoR) defined as the time from first response to LM progression.
3. Determination of progression free survival (PFS) [ Time Frame: 12 months ]
   Determine progression free survival (PFS) defined as the time from first treatment to date of LM progression or death from any cause.
4. Overall survival (OS) [ Time Frame: 12 Months ]
   Determine the overall survival (OS) define as the time from first treatment to date of death.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. At least 18 years of age at time of screening.
2. Ability to understand the purposes and risks of the study and has signed a written informed consent document approved by the site-specific IRB.

3. Subject has proven and documented LM that meets the requirements for the study:

   • EANO-ESMO Clinical Practice Guidelines Type 1 and 2 (with the exception of 2D) LM of any primary type.

4. Karnofsky performance status of 60 to 100

5. Acceptable liver function:

   • Bilirubin ≤ 1.5 times upper limit of normal

   • AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal for subjects with normal liver.

     * AST (SGOT) and ALT (SGPT) ≤ 5.0 times upper limit of normal for subjects with liver metastasis

   • Acceptable renal function with serum creatinine ≤ 2 times upper limit of normal

6. Acceptable hematologic status (without hematologic support):

   • ANC ≥1000 cells µL
   • Platelet count ≥75,000/µL
   • Hemoglobin ≥9.0 g/dL
7. All women of childbearing potential must have a negative serum pregnancy test at screening. 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 IUD) with their partner from entry into the study through 6 months after the last dose.
8. Subjects with a creatinine clearance greater than or equal to 60 mL/min (using the Cockcroft-Gault Equation) for males and females.

Exclusion Criteria:

1. The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study.
2. Obstructive or symptomatic communicating hydrocephalus
3. Ventriculo-peritoneal or ventriculo-atrial shunts without programable valves or contraindications to placement of Ommaya reservoir
4. Females of childbearing potential who are pregnant, breast feeding, or may possibly be pregnant without a negative serum pregnancy test
5. Serious intercurrent illness, such as progressive systemic (extra leptomeningeal) disease, clinically significant cardiac arrhythmias, 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, seizure disorder with any seizure occurring within 14 days prior to consenting or encephalopathy
6. Active severe non hematologic organ toxicity such as renal, cardiac, hepatic, pulmonary, or gastrointestinal systemic toxicity grade 3 or above.
7. Significant coagulation abnormalities such as inherited bleeding diathesis or acquired coagulopathy with unacceptable risks of bleeding.
8. Patients who had any dose to the spinal cord or whole brain radiation therapy, regardless of when the radiation treatment was delivered.
9. Myelopathy following spinal irradiation greater than 3 weeks prior to the first dose of 186RNL.
10. Systemic chemotherapeutic agents with CNS penetration (such as temozolomide, carmustine, lomustine, capecitabine, carboplatin, vinorelbine, bevacizumab, irinotecan or topotecan) unless they develop or have progressive or persistent leptomeningeal metastases while on these agents.
11. Systemic therapy (including investigational agents and small-molecule kinase inhibitors) within 14 days or 5 half-lives, whichever is shorter, prior first dose of study drug (186RNL).
12. 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 (186RNL).
13. Impaired CSF Flow Study performed on Day -4 to Day -2 based on study imaging and as determined by the investigator.

Contacts and Locations

Contacts

Contact: Melissa Moore, PhD; 1-347-570-3338; MMoore@plustherapeutics.com

Contact: Norman LaFrance, MD (CMO); 1-215-808-0955; nlafrance@plustherapeutics.com

Locations

United States, Texas

Universiy of Texas Southwestern Medical Center; Recruiting

Dallas, Texas, United States, 75390

Contact: Omar Raslan 214-648-6691 omar.raslan@utsouthwestern.edu

Principal Investigator: Michael Youssef, MD

UT Health Science Center San Antonio / Mays Cancer Center; Recruiting

San Antonio, Texas, United States, 78229

Contact: Epp Goodwin 210-450-5798

Principal Investigator: Andrew J Brenner, M.D., Ph.D.

Sub-Investigator: William T Phillips, M.D.

Sub-Investigator: John Floyd, M.D.

Sub-Investigator: Eva Galvan, M.D.

Sponsors and Collaborators

Plus Therapeutics

Investigators

• Study Chair: Marc Hedrick, MD; Plus Therapeutics, President and CEO

More Information

• Responsible Party: Plus Therapeutics
• ClinicalTrials.gov Identifier: NCT05034497
• Other Study ID Numbers: 2021-LM-001
• First Posted: September 5, 2021
• Last Update Posted: December 8, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasm Metastasis; Meningeal Carcinomatosis; Neoplastic Processes; Neoplasms; Pathologic Processes; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases