Clinical Trials /

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

NCT03995706

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Glioblastoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Neuro/Sacituzumab Govitecan/Breast Brain Metastasis/Glioblastoma/Ph 0
  • Official Title: A Phase 0, Investigator Initiated Study to Determine the Bioavailability of Sacituzumab Govitecan in Breast Brain Metastasis and Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: CTMS# 19-0069
  • SECONDARY ID: HSC20190378H
  • NCT ID: NCT03995706

Conditions

  • Glioblastoma

Interventions

DrugSynonymsArms
Sacituzumab GovitecanBreast Brain Metastasis and Glioblastoma

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Breast Brain Metastasis and GlioblastomaExperimentalSacituzumab 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.
  • Sacituzumab Govitecan

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Ratio of SN-38 and its metabolites relative to serum concentration
Time Frame:Day 1 of each 21 day cycle
Safety Issue:
Description: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.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:The University of Texas Health Science Center at San Antonio

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