Sacituzumab Govitecan in Treating Patients with Breast Cancer Brain Metastasis or Recurrent Glioblastoma
This early phase I trial studies the extent by which sacituzumab govitecan is able get into the brain in treating patients with breast cancer that has spread to the brain (brain metastasis) or glioblastoma that has come back after previous treatment (recurrent). Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug called govitecan. Sacituzumab attaches to TROP2 positive tumor cells in a targeted way and delivers govitecan to kill them.
Inclusion Criteria
- Histologically or cytologically documented breast cancer of all subtypes including hormone receptor positive, HER2 positive, and triple negative (cohort A) with known or suspected parenchymal brain metastases
- Recurrent glioblastoma (cohort B) with documented progression by Response Assessment in Neuro-Oncology (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
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Life expectancy of at least 3 months
- Bilirubin =< 1.5 times upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 3.0 times upper limit of normal (ULN)
- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 times ULN
- Calculated creatinine clearance >= 30 mL/minute according to the Cockcroft and Gault formula
- Absolute neutrophil count (ANC) >= 1500 cells/uL (without hematologic support)
- Platelet count >= 100,000/uL (without hematologic support)
- Hemoglobin >= 9.0 g/dL (without hematologic support)
- 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 intrauterine device [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 magnetic resonance imaging (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 (e.g., has pacemaker)
- The subject has received enzyme-inducing anti-epileptic agents within 14 days of study drug (e.g., 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 electrocardiography (ECG) abnormality, including: * Marked baseline prolonged QT/corrected QT (QTc) interval (i.e., a repeated demonstration of a QTc interval > 500 ms) demonstrated on ECG at screening * History of risk factors for torsade de pointes (e.g., 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
- Patients with leptomeningeal carcinomatosis are excluded
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03995706.
PRIMARY OBJECTIVE:
I. To determine the extent by which sacituzumab govitecan is able to penetrate the blood brain barrier and access tumor tissue by testing for free SN-38, SN-38G and total SN-38 concentrations in tumor tissue as well as in cerebrospinal fluid (CSF) (if available) and serum samples.
SECONDARY OBJECTIVES:
I. To determine the progression-free survival after debulking craniotomy for patients treated with sacituzumab govitecan in patients with breast brain metastatic tumors and glioblastoma.
II. To determine overall survival after debulking craniotomy for patients treated with sacituzumab govitecan in patients with breast brain metastatic tumors and glioblastoma.
III. To assess the safety of sacituzumab govitecan in breast brain metastatic tumors and glioblastoma.
EXPLORATORY OBJECTIVE:
I. Correlate tumoral total SN-38 and free SN-38 with tumoral hypoxia and tumoral Trop-2 expression.
OUTLINE:
Prior to surgery, patients receive sacituzumab govitecan intravenously (IV) over 3 hours on day -1. Beginning 21 days after surgery, patients receive sacituzumab govitecan IV over 1-3 hours on days 1 and 8. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who have not progressed after 6 cycles may be permitted to continue therapy on a case-by-case basis. Patients also have the option to undergo CSF collection via lumbar puncture on day 8 of cycle 1.
After completion of study treatment, patients are followed for 30 days and then every 3 months for up to 1 year.
Trial PhasePhase O
Trial Typetreatment
Lead OrganizationCancer Therapy and Research Center at The UT Health Science Center at San Antonio
Principal InvestigatorAndrew Jacob Brenner
- Primary IDCTMS 19-0069
- Secondary IDsNCI-2019-05154, HSC20190378HU
- ClinicalTrials.gov IDNCT03995706