TH-302 in Combination With Bevacizumab for Glioblastoma

A Phase 2, Investigator Initiated Study to Determine the Safety and Efficacy of TH-302 in Combination With Bevacizumab for Glioblastoma Following Bevacizumab Failure

Dual center, single arm, two-stage, non-blinded, prospective study of combination therapy bevacizumab at 10mg/kg and TH-302 at 670mg/m2 every 2 weeks (6 week cycle) until disease progression.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Bevacizumab; Drug: TH-302

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • 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
• Genders Eligible for Study: All

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 glioblastoma
• Progression following both standard combined modality treatment with radiation and temozolomide chemotherapy, as well as bevacizumab
• Recovered from toxicities of prior therapy to grade 0 or 1
• ECOG performance status ≤ 2
• Life expectancy of at least 3 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. Serum creatinine ≤ULN

• 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

Exclusion Criteria:

• 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, 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) v4.03 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 has evidence of wound dehiscence
• Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation <90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause normal tissue hypoxia
• The subject is pregnant or breast-feeding.

• The subject has serious intercurrent illness, such as:

  1. hypertension (two or more blood pressure [BP] readings performed at screening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment
  2. non-healing wound, ulcer, or bone fracture
  3. significant cardiac arrhythmias
  4. untreated hypothyroidism
  5. uncontrolled active infection
  6. symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug
  7. myocardial infarction, stroke, transient ischemic attack within 6 months
  8. gastrointestinal perforation, abdominal fistula, intra- abdominal abscess within 1 year
  9. history or clinical evidence of pancreatitis within 2 years
• The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.

• The subject has received any of the following prior anticancer therapy:

  1. Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy, or intra-operative radiotherapy (IORT). Note: stereotactic radiosurgery (SRS) is allowed
  2. Non-bevacizumab 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
  3. Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug
  4. 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
  5. Prior treatment with carmustine wafers
  6. Prior treatment with TH-302

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: Bevacizumab and TH-302; Patients will be treated with combination of bevacizumab and TH-302.	Drug: Bevacizumab; 10mg/kg; Other Names: Avastin; Drug: TH-302; 670mg/m2; Other Names: MSC2491899A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Adverse Events	Safety lab tests and adverse event assessment	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression of disease by RANO criteria: The RANO criteria divides response into four types of response based on imaging and clinical features; complete response; partial response; stable disease; progression	4 months

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Investigators: Principal Investigator: Andrew Brenner, MD, University of Texas Health Science Center San Antonio at the Cancer Therapy and Research Center

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): January 4, 2019
• Study Completion (Actual): December 4, 2019

Study Registration Dates

• First Submitted: January 14, 2015
• First Submitted That Met QC Criteria: January 16, 2015
• First Posted (Estimate): January 19, 2015

Study Record Updates

• Last Update Posted (Actual): April 10, 2020
• Last Update Submitted That Met QC Criteria: April 9, 2020
• Last Verified: April 1, 2020

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; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: CTRC 12-0105; HSC20130212H (Other Identifier: UT Health Science Center Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No