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TH-302 in Combination With Bevacizumab for Glioblastoma

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT02342379
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

The University of Texas Health Science Center at San Antonio
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Andrew Brenner, MD
Principal Investigator Affiliation University of Texas Health Science Center San Antonio at the Cancer Therapy and Research Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioblastoma
Arms & Interventions

Arms

Experimental: Bevacizumab and TH-302

Patients will be treated with combination of bevacizumab and TH-302.

Interventions

Drug: - Bevacizumab

10mg/kg

Drug: - TH-302

670mg/m2

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Dana-Farber Cancer Institute, Boston, Massachusetts

Status

Address

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

San Antonio, Texas

Status

Address

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

San Antonio, Texas, 78229