Status:

COMPLETED

Safety and Efficacy Study of TH-302 CNS Penetration in Recurrent High Grade Astrocytoma Following Bevacizumab

Lead Sponsor:

The University of Texas Health Science Center at San Antonio

Conditions:

HIGH GRADE GLIOMA

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

The Primary Objectives are: * To determine the extent by which TH-302 is able to penetrate the blood brain barrier and affect tumor tissue * To assess the safety of single dose TH-302 in patients wit...

Detailed Description

Single center, dose-escalation, prospective study with TH-302 single dose at 575 mg/m2 or placebo administered preoperatively, followed by postoperative combination therapy bevacizumab at 10mg/kg ever...

Eligibility Criteria

Inclusion

  • 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 both standard combined modality treatment with radiation and temozolomide chemotherapy, as well as anti-angiogenic therapy (ie, bevacizumab)
  • Recovered from toxicities of prior therapy to grade 0 or 1
  • ECOG performance status of 0 or 1
  • Life expectancy of at least 3 months
  • Acceptable liver function
  • Acceptable renal function
  • Acceptable hematologic status
  • 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

  • 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) v4.0 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 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
  • The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.
  • 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
  • Antiangiogenic agents whose primary mode of action is through the VEGF signaling within 21 days prior to first dose of study drug (surgical subjects only)
  • 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
  • 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
  • Prior treatment with TH-302

Key Trial Info

Start Date :

June 1 2011

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

October 1 2015

Estimated Enrollment :

28 Patients enrolled

Trial Details

Trial ID

NCT01403610

Start Date

June 1 2011

End Date

October 1 2015

Last Update

July 24 2019

Active Locations (1)

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Cancer Therapy & Research Center at UTHSCSA

San Antonio, Texas, United States, 78229