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

NCT03032484 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CTMS# 16-0136
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Astrocytoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Incidence, Nature and Severity of Adverse Events and Serious Adverse Events, Graded According to NCI - Common Toxicity Criteria for Adverse Events Version (4.03)

  Up to 6 28-day cycles

Other Outcomes (1)

• Metabolic Change Analysis of Tumor Tissue by MRS (Magnetic Resonance Spectroscopy)

  Cycle 2: approximately 56 days

Study Arms (2)

Bevacizumab and TVB-2640

EXPERIMENTAL

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; Drug: TVB-2640

Bevacizumab for Cycle 1, then Bevacizumab and TVB-2640

EXPERIMENTAL

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; Drug: TVB-2640

Interventions

Bevacizumab DRUG

Bevacizumab is FDA approved as a treatment for recurrent Glioblastoma following failure of radiation therapy and temozolomide.

Also known as: Avastin

Bevacizumab and TVB-2640; Bevacizumab for Cycle 1, then Bevacizumab and TVB-2640

TVB-2640 DRUG

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.

Bevacizumab and TVB-2640; Bevacizumab for Cycle 1, then Bevacizumab and TVB-2640

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

University of Texas Health Science Center San Antonio at the Cancer Therapy and Research Center

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Astrocytoma

Interventions

Bevacizumab; TVB-2640

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Andrew Brenner, MD
• Organization: University of Texas Health San Antonio

brennera@uthscsa.edu

210-562-4090

Study Officials

• Andrew Brenner

  UT Health San Antonio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2017
• First Posted: January 26, 2017
• Study Start: May 18, 2017
• Primary Completion: April 4, 2020
• Study Completion: April 5, 2021
• Last Updated: June 15, 2023
• Results First Posted: June 15, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)