Sacituzumab Govitecan in Recurrent Glioblastoma

Study Overview
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Brief Summary
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This is an open-label single arm study. All patients will receive the investigational agent.

Official Title
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A Phase II, Multicenter, Prospective Study of Sacituzumab Govitecan in Recurrent Glioblastoma

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Sacituzumab Govitecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 (de novo) GBM 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 therapy is not exclusionary. No additional lines of therapy. 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 three 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: a. 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 Exclusion Criteria: 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. 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). The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered prior to study drug. The subject is pregnant or breast-feeding. 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 untreated hypothyroidism unhealed rectal or peri-rectal abscess uncontrolled active infection symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug any history of cardiac arrhythmia or heart block stroke or transient ischemic attack within 6 months 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 Patients with radiographically apparent leptomeningeal involvement are excluded

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sacituzumab govitecan<br>Dosing will be at 10 mg/kg on days 1 and 8 of a 21-day cycle | Drug: Sacituzumab Govitecan<br>* Sacituzumab Govitecan will be administered by IV infusion over 3 hours for first administration and over 1 hour if tolerated. Subjects will be allowed to continue treatment until they have evidence of significant treatment-related toxicity or progressive disease.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | A single-arm two-stage Phase II Bayesian adaptive study of Sacituzumab Govitecan will be carried out in the expansion phase based on progression free survival at 6 months with unfavorable and favorable probabilities of 0.17 and 0.34, respectively. | 6 months |