Pro00044274 CTO with Bevacizumab

Clinical Trials for Adults | A Phase I/II Trial of Carboxyamidotriazole Orotate (CTO) Alone or in Combination with Bevacizumab for Adult Patients with Recurrent Malignant Glioma Post-Bevacizumab Failure

Primary Objectives

  • To determine the maximum tolerated dose (MTD) of CTO when combined with standard dosing of bevacizumab among patients with recurrent malignant glioma (WHO grade 3 or 4) that have previously failed bevacizumab (Phase 1);
  • To determine the activity of CTO alone in bevacizumab-failure WHO grade IV malignant glioma patients (Phase 2, Arm 1);
  • To determine the activity of CTO plus bevacizumab in bevacizumab-failure WHO grade IV malignant glioma patients (Phase 2, Arm 2).

Inclusion

  • Phase 1 portion: Patients must have recurrent histologically confirmed diagnosis of WHO grade III or IV malignant glioma with no more than 3 prior progressions.
  • Phase 2 portion: Patients must have recurrent histologically confirmed diagnosis of WHO grade IV malignant glioma (glioblastoma or gliosarcoma) with no more than 3 prior progressions.
  • Must have had a least 1 prior progression on a bevacizumab-containing regimen.
  • Karnofsky ≥ 60%
  • Bi-dimensionally measurable disease, as assessed by magnetic resonance imaging based on RANO criteria
  • For patients on corticosteroids, they must be on a stable dose for 7 days prior to anticipated start of study drug, and the dose should not be escalated over entry dose level, if clinically possible.

Exclusion

  • Taking strong or moderate CYP3A4 inhibitors and inducers
  • Treated with immunotherapeutic agents or vaccines within 4 weeks before enrollment or have not recovered from the toxic effects of such cancer therapy.
  • Treated with alkylating agents within 4 weeks before enrollment or treated with daily or metronomic chemotherapy within 1 week before enrollment, unless the patient has recovered from the expected toxic effects of such cancer therapy.
  • Prior chemotherapy (non-alkylating agents) within 2 weeks before enrollment or has not recovered from the toxic effects of such cancer therapy.
  • Prior history of hypertensive crisis, hypertensive encephalopathy, reverse posterior leukoencephalopathy syndrome (RPLS).
  • Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade 2 or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment.
  • Current or recent (within 10 days of study enrollment) use of aspirin (>325 mg/day), clopidogrel (>75 mg/day) or equivalent.  Prophylactic or therapeutic LMWH is allowed.

Treatment Plan

  • CTO given orally on continuous daily dosing schedule starting on Day 1 until progression of disease or intolerance
  • Bevacizumab (10mg/kg) will be administered intravenously every 2 weeks, starting on Day 1, until progression of disease or intolerance
  • Treatment cycle is 28 days
  •  MRI is every 8 weeks

 





This article comes from The Preston Robert Tisch Brain Tumor Center at Duke   http://www.cancer.duke.edu/btc
The URL for this story is:   http://www.cancer.duke.edu/btc/modules/ClinicalTrials4/index.php?id=117