A Study of 131I-TM601 in Adults With Recurrent Malignant Glioma

A Phase 1/2 Multi-Center, Safety and Efficacy Study Evaluating Intravenously Administered 131I-TM601 in Patients With Progressive and/or Recurrent Malignant Glioma

The purpose of this study is to evaluate the safety and effectiveness of 131I-TM601 in the treatment of adult patients with progressive or recurrent malignant gliomas.

This is a multi-center, open label, non-randomized, Phase 1/2 study evaluating the use of multiple intravenous doses of 131I-TM601 in patients with progressive and/or recurrent malignant glioma.

The study will be conducted in two phases. Prior to initiating treatment as part of this study, patients will be administered a single imaging dose of 131I-TM601, IV, to demonstrate tumor uptake. Only patients demonstrating tumor uptake will remain on the study. During the first, Dose Escalation Phase of the study, eligible patients will be assigned in groups of 3-6 (depending upon the treatment response seen at each dose) to dose cohorts of between 2-5 weekly IV doses of 131I-TM601, with escalation to the next highest dose dependent upon demonstrated tolerance in the previous dosing group. Patients enrolled in the second phase will be assigned to a dose determined by the experience in the first phase.

Patients in both study phases will have safety parameters evaluated continuously throughout the study. Clinical response to 131I-TM601 will be assessed in each study patient at 28 days following the final study dose, and then at quarterly intervals scheduled at 3 month intervals following the first study dose, until disease progression.

Inclusion Criteria:

Patients must:

1. Have histologically proven malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma or glioblastoma multiforme) which is progressive and/or recurrent after external beam radiation therapy (to at least 50 Gy) ± chemotherapy with or without a history of surgical resection. Patients with previous low grade glioma who progressed after radiotherapy ± chemotherapy and are biopsied and found to have a high grade glioma are eligible. Patients with prior therapy that included interstitial brachytherapy, stereotactic radiosurgery, or local radiopharmaceutical injection must have confirmation of true progressive disease rather than radiation necrosis based upon PET or Thallium scanning or pathological documentation of disease.

2. Have bi-dimensional measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 2 planes on post-contrast MRI.

   Note - a CT scan will be acceptable in place of an MRI only in patients who are unable to undergo an MRI.

3. Be ≥18 years of age.

4. Have a baseline Karnofsky Performance Status (KPS) of ≥60%.

5. Have a Mini Mental State Exam score of ≥ 19.

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

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

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

9. 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.

10. Have adequate organ and marrow function as defined by serum chemistry evaluations (defined in study protocol).

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

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

13. Agree to refrain from nursing, if female.

14. Have signed and dated written informed consent.

15. 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 include, but are 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. Have received radiation treatments ≤ 3 months prior to first study drug administration (Imaging Dose).
4. Have received any cytotoxic chemotherapy, whether conventional or investigational, ≤ 4 weeks prior to receiving the first study drug (Imaging Dose) administration in this study (6 weeks for mitomycin-C or nitrosoureas).
5. Have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to 131I-TM601 e.g. iodine or iodine-containing drugs.