Neuro/Sacituzumab Govitecan/Breast Brain Metastasis/Glioblastoma/Ph 0

A Phase 0, Investigator Initiated Study to Determine the Bioavailability of Sacituzumab Govitecan in Breast Brain Metastasis and Glioblastoma

Single center, non-randomized, Phase 0 study. Sacituzumab Govitecan given preoperatively, followed by craniotomy with surgery or biopsy of brain tumors (GBM and metastatic brain tumors from Breast) and intraoperative tissue collection will follow with contemporaneous CSF (depending on tumor location) and whole blood (serum) sampling.

Study Overview

• Status: Active, not recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Sacituzumab Govitecan

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Mays Cancer Center, UT Health San Antonio

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• At least 18 years of age
• Histologically or cytologically documented breast cancer (Cohort A) with known or suspected parenchymal brain metastases.
• Recurrent glioblastoma (Cohort B) with documented progression by RANO criteria following standard combined modality treatment with radiation and temozolomide.
• Plans to undergo craniotomy as part of standard of care. Patients emergently needing surgical debulking due to symptoms of their disease are not eligible.
• Recovered from toxicities of prior therapy to grade 0 or 1
• ECOG performance status ≤ 2.
• Life expectancy of at least 3 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);
• Adequate renal function: calculated creatinine clearance ≥30mL/minute according to the Cockcroft and Gault formula
• Acceptable hematologic status (without hematologic support)
• ANC ≥1500 cells/uL
• Platelet count ≥100,000/uL
• Hemoglobin ≥9.0 g/dL
• 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.

Exclusion Criteria:

• The subject is receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin (LMWH) before the first dose of study drug.
• 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.
• The subject is unable to undergo MRI scan (eg, has pacemaker).
• The subject has received enzyme-inducing anti-epileptic agents within 14 days of study drug (eg, carbamazepine, phenytoin, phenobarbital, primidone).
• Patients whose only lesion undergoing resection has received stereotactic radiation within the past 3 months

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

  • Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug
  • Prior treatment with Sacituzumab Govitecan
• Patients receiving UGT1A1 (Uridine diphosphate glucuronosyl transferase 1A1) inhibitors or inducers.

• History of significant cardiovascular disease, defined as:

  • Congestive heart failure greater than New York Heart Association (NYHA) Class II according to the NYHA Functional Classification.
  • Unstable angina or myocardial infarction within 6 months before enrollment.
  • Serious cardiac arrhythmia.

• Clinically significant ECG abnormality, including:

  • Marked Baseline prolonged QT/QTc interval (ie, a repeated demonstration of a QTc interval >500 ms) demonstrated on ECG at Screening.
  • History of risk factors for torsade de pointes (eg, heart failure, hypokalemia, family history of long QT Syndrome).
• Any medical or other condition which, in the opinion of the Investigator, causes the subject to be medically unfit to receive Sacituzumab Govitecan, or unsuitable for any other reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Breast Brain Metastasis and Glioblastoma; Sacituzumab Govitecan treatment will be initiated with a 10mg/kg standard dose without any dose escalation on day-1, prior to surgery. Sacituzumab govitecan and will continue to be administered by IV infusion over 3 hours on Days 1 and 8 of a 21 day cycle post-operatively until progression.	Drug: Sacituzumab Govitecan; All 20 subjects will receive study drug Sacituzumab Govitecan preoperatively. Intraoperative tissue collection will follow with contemporaneous CSF (depending on tumor location) and whole blood (serum) sampling. Samples will be tested for total SN-38and free SN-38, as well as SN-38G. Following recovery from surgery, patients will resume treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of SN-38 and its metabolites relative to serum concentration	Levels of SN-38 and its metabolites will be measured and a ratio calculated relative to the serum concentration of SN-38 and its metabolites. The ratio will show the amount of investigational product that crosses the blood brain barrier to reach the tumor.	Day 1 of each 21 day cycle

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: Andrew Brenner, MD, PhD, University of Texas Health at San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2019
• Primary Completion (Actual): June 3, 2022
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: June 17, 2019
• First Submitted That Met QC Criteria: June 20, 2019
• First Posted (Actual): June 24, 2019

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Glioblastoma; Brain Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Immunoconjugates; Sacituzumab govitecan
• Other Study ID Numbers: CTMS# 19-0069; HSC20190378H (Other Identifier: UT Health Science Center Institutional Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No