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A Phase I Dose Escalation Study Evaluating the Safety and Biologically Active Dose of TM-601 Based on Perfusion MRI Imaging Criteria in Patients With Progressive and/or Recurrent Malignant Glioma

Phase 1
18 Years
Open (Enrolling)
Malignant Glioma, Glioblastoma Multiforme, GBM, Astrocytoma, Oligodendroglioma

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Trial Information

A Phase I Dose Escalation Study Evaluating the Safety and Biologically Active Dose of TM-601 Based on Perfusion MRI Imaging Criteria in Patients With Progressive and/or Recurrent Malignant Glioma

This Phase I study will evaluate the safety of TM-601 in patients with recurrent malignant
glioma who have failed first-line, standard therapy.

Study patients will be assigned to receive treatment in 1 of 6 treatment cohorts. Patients
will be assigned to each dose level in groups of 3-6 (depending upon treatment response seen
within each cohort), with escalation to the next highest dose dependent upon demonstrated
tolerance in the previous dosing group.

Patients will be administered an imaging dose of 131I-TM-601, intravenously, to demonstrate
tumor-specific localization prior to study treatment with non-labeled TM-601. Eligible
patients demonstrating tumor-specific imaging will be assigned to a treatment cohort and
will received non-labeled TM-601 once a week for 3 weeks, followed by clinical follow-up
visits and MR imaging.

Data from this study will help determine the IV dose of TM-601 required to produce MR
perfusion changes (as well as other biomarker changes) in patients with recurrent malignant
glioma. It is not known whether participation in this trial will provide patients with
benefit in terms of improved tumor control, although pre-clinical evidence and evidence from
other clinical trials with 131I TM-601 suggest that TM-601 is an active agent in malignant

Inclusion Criteria:

Patients Must:

1. Have histologically proven malignant glioma (anaplastic astrocytoma, anaplastic
oligodendroglioma or glioblastoma multiforme) which is progressive or recurrent after
external beam radiation therapy (to at least 50 Gy) ± chemotherapy. Patients with
previous low grade glioma who progressed after radiotherapy ± chemotherapy and are
biopsied and found to have a high grade glioma are eligible.

2. Be ≥18 years of age.

3. Have a baseline Karnofsky Performance status of ≥60%

4. Have a Mini Mental State Exam score ≥ 19.

5. Have a life expectancy, based on the Investigator's judgment, of >3 months.

6. On screening ECG, have a QTc interval of <450 ms.

7. If taking steroids, be on a dose that is stable for at least 5 days prior to the
imaging dose.

8. Have recovered from the toxicity of all previous therapy prior to enrollment. If the
patient has undergone recent major surgery, an interval of at least 3 weeks must have
elapsed between the surgery and the date of the imaging dose.

9. Have adequate organ and marrow function as defined below:

hemoglobin >9.0g/dL absolute neutrophil count >1,500 mm3 platelet count >100,000 mm3
prothrombin time <1.5 ULN partial thromboplastin time (PTT) <1.5 ULN total
bilirubin < 2.0 mg/dL AST(SGOT)/ALT(SGPT) <5 x institutional ULN creatinine (serum)
≤2.0 mg/dL*

*If serum creatinine is >2.0 then creatinine clearance must be ≥60 ml/min

10. Have a negative serum and urine pregnancy test within 14 days of study drug
administration, if female and of child bearing potential.

11. Agree to use an effective form of contraception to avoid pregnancy, if fertile
(applicable to both male and female patients).

12. Agree to refrain from nursing, if female.

13. Have signed and dated written informed consent.

14. Be able to comply with treatment plan, study procedures and follow-up examinations.

Exclusion Criteria:

Patients may NOT:

1. Have a serious concurrent infection or medical illness which would jeopardize the
ability of the patient to receive the treatment outlined in this protocol with
reasonable safety. (Examples of medical illnesses are [but not limited to] the
following: uncontrolled hypertension, symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that
would limit compliance with study requirements.)

2. Have a prior malignancy with less than 5-year disease free interval, except for
adequately treated basal cell or squamous cell carcinoma of the skin, or in situ
cancer of the cervix.

3. Be pregnant or breast-feeding.

4. Have received radiation treatments ≤ 3 months from time of first study drug

5. Have received any cytotoxic chemotherapy, whether conventional or investigational, ≤
4 weeks prior to enrollment in this study (6 weeks for mitomycin-C or nitrosoureas).

6. Have a history of allergic reactions attributed to compounds of similar chemical or
biologic composition to 131I-TM-601 e.g. iodine or iodine-containing drugs.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the safety profile/tolerability of TM-601 in this patient population, based on adverse event incidence, severity, duration, causality, seriousness and type as well as by physical examination, vital signs and clinical laboratory assessments.

Outcome Time Frame:

Throughout the treatment phase of the study for each study patient, and for 28 days following the final study dose.

Safety Issue:


Principal Investigator

Burt Nabors, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Alabama at Birmingham


United States: Food and Drug Administration

Study ID:




Start Date:

February 2008

Completion Date:

February 2010

Related Keywords:

  • Malignant Glioma
  • Glioblastoma Multiforme
  • GBM
  • Astrocytoma
  • Oligodendroglioma
  • recurrent glioma
  • Phase I
  • Multi-Center
  • Open label
  • Brain Cancer
  • Brain tumor
  • GBM
  • Glioma
  • Glioblastoma multiforme
  • Astrocytoma
  • Glioblastoma
  • Glioma
  • Oligodendroglioma



Wake Forest University Winston-Salem, North Carolina  27103
University of Alabama Birmingham, Alabama  
Cedars-Sinai Medical Center Los Angeles, California  90048
University of Washington Seattle, Washington  98195
Columbia University New York, New York  10032-3784
Northwestern University Chicago, Illinois  60611
Washington University St. Louis, Missouri  63110