Phase I Trial of Arsenic Trioxide and Stereotactic Radiotherapy for Recurrent Malignant Glioma

Not Recruiting

Trial ID: NCT00185861


To investigate the safety of delivering arsenic trioxide (ATO) in combination with stereotactic radiotherapy in recurrent malignant glioma by performing an open label, Phase I dose escalation trial. Results from this study will provide a basis for further study of ATO combined with radiation therapy as a radiosensitizer for malignant brain tumors in future Phase II studies.

Official Title

Phase I Trial of Arsenic Trioxide and Stereotactic Radiotherapy for Recurrent Malignant Glioma

Stanford Investigator(s)

Iris C. Gibbs, MD, FACR, FASTRO
Iris C. Gibbs, MD, FACR, FASTRO

Professor of Radiation Oncology (Radiation Therapy) and, by courtesy, of Neurosurgery

Paul Graham Fisher, MD
Paul Graham Fisher, MD

Beirne Family Professor of Pediatric Neuro-Oncology, Professor of Pediatrics and, by courtesy, of Neurosurgery and of Epidemiology and Population Health

Lawrence Recht, MD
Lawrence Recht, MD

Professor of Neurology (Adult Neurology) and, by courtesy, of Neurosurgery

Huy M. Do, MD
Huy M. Do, MD

Professor of Radiology (Neuroimaging and Neurointervention) and, by courtesy, of Neurosurgery and of Otolaryngology - Head & Neck Surgery (OHNS)


Inclusion Criteria:

   - Evidence of recurrent disease.

   - All patients will have received previous conventional radiotherapy at least 3 weeks
   prior to enrollment. Histologic verification of malignant glioma is required. If the
   initial primary brain tumor was histologically malignant glioma and subsequent
   contrast enhanced MRI imaging shows tumor consistent with recurrence, additional
   biopsy or surgery is not required. However, if a low-grade neoplasm was the initial
   histologic diagnosis, tissue confirmation of malignant glioma is required at the time
   of recurrence.

   - Age: Patients must be >18 years of age

   - Patients must have a Karnofsky >60%, and/or ECOG performance status <2

   - Patients must have an estimated life expectancy of greater than 8 weeks.

   - Patients must have normal organ and marrow functions as defined below:

      - Leukocytes >3,000/¼l

      - Absolute neutrophil count >1,500/¼l

      - Hemoglobin > 10 gm/dl

      - Platelets >100,000/¼l (transfusion independent)

      - Total bilirubin within normal institutional limits

      - AST (SGOT)/ALT (SGPT) <1.5 X institutional upper limit of normal

      - Creatinine within normal institutional limits OR

      - Creatinine clearance >60mL/min/1.73 m2 for patients with creatinine levels above
      institutional normal

      - Serum potassium* e 4.0mEq/L

      - Serum magnesium* e 1.8mEq/L

      - Serum calcium* within the institutional normal range (should be corrected if low

      - Electrocardiogram Normal

      - electrocardiogram with a rate corrected QT interval (QTc) <500 msec

      *Oral or intravenous supplementation may be used to normalize serum electrolytes

      - Phase I ATO Stereotactic Radiotherapy for Recurrent Malignant Glioma 16 of 44

   - Informed consent All patients or their legal guardians must sign a document of
   informed consent indicating their understanding of the investigational nature of this
   study and the risks involved prior to any protocol related are performed (which does
   not include imaging and laboratory studies that help to establish eligibility).

Exclusion Criteria:- Patients who have had chemotherapy or conventional radiotherapy within
3 weeks of enrollment.

   - Patients who have received prior radiosurgery or stereotactic radiotherapy within 10mm
   of the current target tumor.

   - Patients may not be receiving any other investigational agents.

   - Patients who cannot undergo MRI or CT are not eligible as MRI will be used to confirm
   the diagnosis and CT will be used for treatment planning.

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to arsenic trioxide or other agents used in study.

   - Patients who are taking substances known to prolong the QT interval, see Appendix B.
   If the QT prolonging drug is discontinued and switched to an alternative agent, the
   patients will be allowed to enroll into this protocol as long the agent has been
   discontinued for a period of at least 2 weeks.

   - Patients currently taking Amphotericin B or related antifungal agents will be excluded
   due to potential for increased renal electrolyte wasting during arsenic trioxide

   - Patients with known second-degree heart block or other cardiac dysfunction. New York
   Heart Association Class II or greater (see Appendix E)

   - Uncontrolled intercurrent illnesses including, but not limited to, ongoing or active
   infection, symptomatic congestive heart failure, unstable angina pectoris, or
   psychiatric illness/social situations that would limit compliance with study
   requirements. Phase I ATO Stereotactic Radiotherapy for Recurrent Malignant Glioma 17
   of 44

   - Patients must not be pregnant or breast-feeding. All patients with the potential for
   pregnancy should be counseled and requested to follow acceptable birth control methods
   (hormonal or barrier method of birth control; abstinence) prior to study entry and for
   the duration of study participation. Patients who are pregnant or breast-feeding will
   be excluded because no information on this agent exists with regard to safety of
   arsenic trioxide for a fetus or breast-feeding infant. Should a woman become pregnant
   or suspect she is pregnant while participating in this study, she should inform her
   treating physician immediately.


drug: Arsenic Trioxide

procedure: Stereotactic radiosurgery

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Laurie Tupper

New Trial Alerts