Sacituzumab Govitecan in Recurrent Glioblastoma

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

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

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Sacituzumab Govitecan

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Epp Goodwin; Phone Number: 210-450-1000; Email: goodwine@uthscsa.edu

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • Cleveland Clinic Taussig Cancer Center
      • Contact: Felicia Williams
      • Principal Investigator: Christine Cordova, MD
  • Texas
    • Dallas, Texas, United States, 75251
      • Recruiting
      • Texas Oncology
      • Contact: Kelly Juniper
      • Principal Investigator: Brian Valliant, MD
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • University of Texas Health Science Center San Antonio at the Cancer Therapy and Research Center
      • Contact: Epp Goodwin; Email: goodwine@uthscsa.edu
      • Contact: William Kelly, MD; Phone Number: 210-450-1000; Email: kellyw@uthscsa.edu
      • Principal Investigator: William Kelly, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

  1. Bilirubin ≤ 1.5 times upper limit of normal
  2. 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):

  1. ANC ≥1500 cells/uL
  2. Platelet count ≥100,000/uL
  3. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sacituzumab govitecan; Dosing will be at 10 mg/kg on days 1 and 8 of a 21-day cycle	Drug: Sacituzumab Govitecan; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Investigators: Principal Investigator: William Kelly, MD, Mays Cancer Center, UT Health San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2022
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: September 16, 2020
• First Submitted That Met QC Criteria: September 16, 2020
• First Posted (Actual): September 22, 2020

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Physiological Effects of Drugs; Immunologic Factors; Immunoconjugates; Sacituzumab govitecan
• Other Study ID Numbers: CTMS# 20-0102; HSC20200576X (Other Identifier: UT Health Science Center San Antonio)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No