TVB- 2640 in Combination With Bevacizumab in Patients With First Relapse of High Grade Astrocytoma

A Phase 2 Investigator Initiated Study to Determine the Efficacy and Safety of TVB- 2640 in Combination With Bevacizumab in Patients With First Relapse of High Grade Astrocytoma

Randomized phase 2 study TVB-2640 in combination with Bevacizumab versus Bevacizumab alone.

Study Overview

• Status: Completed
• Conditions: Astrocytoma
• Intervention / Treatment: Drug: Bevacizumab; Drug: TVB-2640

Detailed Description

Eligible patients will be randomized into 2 separate arms:

• Arm number one will receive Bevacizumab every 2 weeks in combination with TVB-2640 from day 1 until day 28 of the first cycle.
• Arm number two will receive Bevacizumab alone every 2 weeks, from on days 1 and 15 of the first until day 28 of the first cycle.
• MR-Spectroscopy will be obtained on all patients (both arms) at day 28 of first cycle.
• Starting on cycle 2 day 1, all patients will converge to a single arm and will continue to receive bevacizumab every 2 weeks in combination with TVB-2640. Every cycle will last 28 days.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center San Antonio at the Cancer Therapy and Research Center

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 high-grade astrocytoma
• Progression following standard combined modality treatment with radiation and temozolomide chemotherapy
• Recovered from reversible toxicities of prior therapy to Grade 0 or Grade 1
• ECOG Performance Status of 0 to 2
• Life expectancy of at least 3 months
• Adequate renal and liver function: AST/ALT ≤ 3 x ULN, Bilirubin ≤ 1.5 times ULN, Creatinine ≤ ULN
• Adequate hematologic status (without hematologic support): Hemoglobin ≥ 9 g/dL, ANC ≥ 1500 cells/ml, Platelets ≥ 100,000 cells/ml
• 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 (for example, surgical sterilization or the use of 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 six months after the last dose.

Exclusion Criteria:

• Receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin (LMWH) before the first dose of study drug
• Evidence of acute intracranial or intratumoral hemorrhage either by MRI or CT scan. Subjects with resolving hemorrhage changes punctuate hemorrhage, or hemosiderin are eligible
• Unable to undergo MRI scan (e.g., pacemaker)
• Received enzyme-inducing anti-epileptic agents within 14 days of study drug (e.g., carbamazepine, phenytoin, phenobarbital, primidone)
• Not recovered to a NCI CTCAE v.4.03 Grade ≤ 1 from AEs (except alopecia and lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered prior to study drug
• Evidence of wound dehiscence
• Pregnant or breast-feeding
• Clinically significant Dry Eye or necessary contact lens use
• Serious intercurrent illness such as: Hypertension (two or more blood pressure readings performed at screening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment, Non-healing wound or ulcer, Uncontrolled life threatening cardiac arrhythmias, Untreated hypothyroidism, Uncontrolled active infection, Symptomatic congestive heart failure or unstable angina pectoris within 3 months prior to study drug, Gastrointestinal perforation, abdominal fistula, intra-abdominal abscess within 1 year
• Inherited bleeding diathesis or coagulopathy with the risk of bleeding
• HIV , Hepatitis B or C documented infections
• 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, Non-antiangiogenic therapy (including investigational agents and small molecular kinase inhibitors) within 7 days or 5 half-lives, whichever is shorter, prior to the 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bevacizumab and TVB-2640; Bevacizumab every 2 weeks in combination with TVB-2640 dosed at 100mg/m2 daily (rounded to 50mg tab dose), from day 1 until day 28 of the first cycle.	Drug: Bevacizumab; Bevacizumab is FDA approved as a treatment for recurrent Glioblastoma following failure of radiation therapy and temozolomide.; Other Names: Avastin; Drug: TVB-2640; TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. TVB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN enzyme.
Experimental: Bevacizumab for Cycle 1, then Bevacizumab and TVB-2640; Bevacizumab alone every 2 weeks, on days 1 and 15 until day 28 of the first cycle, and then receive both Bevacizumab and TVB-2640 for the remainder of their participation in this study.	Drug: Bevacizumab; Bevacizumab is FDA approved as a treatment for recurrent Glioblastoma following failure of radiation therapy and temozolomide.; Other Names: Avastin; Drug: TVB-2640; TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. TVB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN enzyme.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival at 6 Months (PFS6)	Survival of participants at 6 months after the start of treatment without their condition becoming any worse. Brain magnetic resonance imaging (MRI) was performed after every even cycle (e.g., C2, C4) during treatment, with tumor response assessed by the investigator for complete response (CR), partial response (PR) and PD according to the Response Assessment in Neuro-oncology (RANO) criteria.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, Nature and Severity of Adverse Events and Serious Adverse Events, Graded According to NCI - Common Toxicity Criteria for Adverse Events Version (4.03)	Number of adverse of any nature are reported as well as the number of adverse events that were classed as grade 3-5 on the NCI - Common Toxicity Criteria for Adverse Events	Up to 6 28-day cycles

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic Change Analysis of Tumor Tissue by MRS (Magnetic Resonance Spectroscopy)	The MRI was performed during cycle 2. This procedure was intended to be outsourced, and MRIs performed locally produced inadequate resolution, so no data analysis was obtained from this measure.	Cycle 2: approximately 56 days

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Investigators: Principal Investigator: Andrew Brenner, UT Health San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2017
• Primary Completion (Actual): April 4, 2020
• Study Completion (Actual): April 5, 2021

Study Registration Dates

• First Submitted: January 24, 2017
• First Submitted That Met QC Criteria: January 24, 2017
• First Posted (Estimated): January 26, 2017

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Astrocytoma; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: CTMS# 16-0136

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