Sacituzumab Govitecan in Recurrent Glioblastoma

Korábbi kezelés

• Prior treatment with bevacizumab or other VEGF inhibitors or VEGF-Receptor signaling inhibitors
• 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.
  • 3 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). 5. The subject has received enzyme-inducing anti-epileptic agents within 14 days of study drug (eg, carbamazepine, phenytoin, phenobarbital, primidone).
• symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug
• stroke or transient ischemic attack within 6 months 8. The subject has received any of the following prior anticancer therapy:
• Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy (RIT), or intra-operative radiotherapy (IORT). Note: stereotactic radiosurgery (SRS) is allowed
• Systemic therapy (including investigational agents and small-molecule kinase inhibitors) or non-cytotoxic hormonal therapy (eg, tamoxifen) within 7 days or 5 half-lives, whichever is shorter, prior first dose of study drug
• Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug
• 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
• Prior treatment with carmustine wafers 9. Patients with radiographically or clinically apparent leptomeningeal involvement are excluded.

Más betegség

• The subject is pregnant or breast-feeding. 7. The subject has serious intercurrent illness, such as:
• hypertension (two or more blood pressure [BP] readings performed at screening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment
• non-healing wound, ulcer, or bone fracture
• significant cardiac arrhythmias
• uncontrolled active infection
• any history of cardiac arrhythmia or heart block

Egyéb

• untreated hypothyroidism
• unhealed rectal or peri-rectal abscess

• At least 18 years of age.
• Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee.
• Histologically confirmed IDH wild type (primary) GBM. Molecular GBM (as per cIMPACT-NOW 3) is allowed as is gliosarcoma and epithelioid glioblastoma. IDH-mutant glioma is not allowed.
• Progression following standard combined modality treatment with radiation and temozolomide chemotherapy if O6-Methylguanine-DNA Methyltransferase (MGMT) methylated.
  • Prior temozolomide is not required for MGMT unmethylated, but patient must have received standard doses of radiation.
  • Inclusion of additional investigational therapy with standard frontline therapy is not exclusionary. No additional lines of therapy given for recurrent disease.
  • Prior tumor-treating field therapy is not excluded, nor considered and additional line of therapy as this is often given concurrently with other therapy lines.
• Patients may have had been operated for recurrence, but if operated must have had surgery a minimum of 2 weeks prior to enrollment and have an MRI completed within 48 hours following surgery.
• No radiotherapy within the 3 months prior to the diagnosis of progression.
• Willingness to forego tumor-treatment field (Optune) therapy during participation in the study.
• Stable or decreasing dosage of steroids for 7 days prior to the baseline MRI scan.
• Recovered from toxicities of prior therapy to grade 0 or 1, except for neuropathy (Grade ≤2) and alopecia.
• ECOG performance status ≤ 2.
• Life expectancy of at least 6 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)
• Acceptable renal function:
  • Creatinine clearance ≥30 mL/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.
• Availability of biological material for central review and biomarker evaluation.
• Untreated recurrent or residual disease that is measurable by RANO criteria at time of enrollment. Multifocal and infratentorial disease is allowed.
• Positive Trop-2 expression (H-Score ≥200), as verified by central review at University of Texas Health Science Center at San Antonio (UTHSA).