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

NCT03995706 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: CTMS# 19-0069HSC20190378H
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Breast Brain Metastasis and Glioblastoma

EXPERIMENTAL

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

Interventions

Sacituzumab Govitecan DRUG

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

Breast Brain Metastasis and Glioblastoma

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
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• Gilead Sciences: collaborator

Study Sites (1)

Mays Cancer Center, UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Balinda HU, Kelly WJ, Kaklamani VG, Lathrop KI, Canola MM, Ghamasaee P, Sareddy GR, Michalek J, Gilbert AR, Surapaneni P, Tiziani S, Pandey R, Chiou J, Lodi A, Floyd JR 2nd, Brenner AJ. Sacituzumab Govitecan in patients with breast cancer brain metastases and recurrent glioblastoma: a phase 0 window-of-opportunity trial. Nat Commun. 2024 Aug 7;15(1):6707. doi: 10.1038/s41467-024-50558-9.

  PMID: 39112464 DERIVED

Related Links

• Open Access publication of results

MeSH Terms

Conditions

Glioblastoma

Interventions

sacituzumab govitecan

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Andrew Brenner, MD, PhD

  University of Texas Health at San Antonio

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 17, 2019
• First Posted: June 24, 2019
• Study Start: July 17, 2019
• Primary Completion: June 3, 2022
• Study Completion: March 20, 2024
• Last Updated: September 4, 2024

Record last verified: 2024-08

Locations

US (1)