TH-302 in Combination With Bevacizumab for Glioblastoma
Condition: Glioblastoma
MeSH terms: Glioblastoma
Intervention: Bevacizumab; TH-302
Intervention description: 10mg/kg; 670mg/m2
Intervention MeSH terms: Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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