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

Sponsor

TransMolecular (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00683761

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Malignant Glioma Glioblastoma Multiforme GBM Astrocytoma Oligodendroglioma	Drug: 131I-TM601	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

64 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2008

Anticipated Primary Completion Date :

Feb 1, 2010

Anticipated Study Completion Date :

Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: 131I-TM601 In the first study phase (Dose Escalation), patients will be assigned to treatment to between 2-5 doses of 131I-TM601 treatment at a treatment dose of 1.2 mCi/kg of lean body mass (in scaled dosing, this will amount to 0.024 mg TM601 peptide/kg of lean body mass), once weekly (for between 2-5 weeks, depending upon dose cohort). The maximum amount of administered radioactivity per infusion is 100 mCi.

Arm

Intervention/Treatment

Experimental: 1

Drug: 131I-TM601

In the first study phase (Dose Escalation), patients will be assigned to treatment to between 2-5 doses of 131I-TM601 treatment at a treatment dose of 1.2 mCi/kg of lean body mass (in scaled dosing, this will amount to 0.024 mg TM601 peptide/kg of lean body mass), once weekly (for between 2-5 weeks, depending upon dose cohort). The maximum amount of administered radioactivity per infusion is 100 mCi.

Outcome Measures

Primary Outcome Measures

The safety and tolerability of multiple doses of intravenously (IV) administered 131I-TM601 in adult patients with progressive and/or recurrent malignant glioma with measurable disease. [Safety will be evaluated throughout the treatment and follow-up phase for all study patients; dose escalation decisions will be based on safety experience for each patient at 21 days following the final treament dose.]
The therapeutic efficacy of multiple doses of IV-administered 131I-TM601, as assessed by clinical response, time-to-progression, 6 month progression-free survival and overall survival in adult patients with progressive and/or recurrent malignant glioma. [At six months following first treatment dose, and until disease progression.]

Secondary Outcome Measures

Radiation absorbed dose to tumor and normal organs from IV administered 131I-TM601 in a subset of study patients. [Assessments timed within 3 days of study doses.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must:

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.
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.

Be ≥18 years of age.
Have a baseline Karnofsky Performance Status (KPS) of ≥60%.
Have a Mini Mental State Exam score of ≥ 19.
Have a life expectancy, based on the Investigator's judgment, of >3 months.
On screening ECG, have a QTc interval of <450 ms.
If taking steroids, be on a dose that is stable for at least 5 days prior to the Imaging Dose.
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.
Have adequate organ and marrow function as defined by serum chemistry evaluations (defined in study protocol).
Have a negative serum pregnancy test within 14 days of study drug administration, if female and of child bearing potential.
Agree to use an effective form of contraception to avoid pregnancy, if fertile (applicable to both male and female patients).
Agree to refrain from nursing, if female.
Have signed and dated written informed consent.
Be able to comply with treatment plan, study procedures and follow-up examinations.

Exclusion Criteria:

Patients may not:

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.
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.
Have received radiation treatments ≤ 3 months prior to first study drug administration (Imaging Dose).
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).
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60637
2	Johns Hopkins University	Baltimore	Maryland	United States	21287
3	St. Mary's Health Care	Grand Rapids	Michigan	United States	49503
4	University of Virginia	Charlottesville	Virginia	United States	22908-0394

Sponsors and Collaborators

TransMolecular

Investigators

Principal Investigator: Karen Fink, MD, Baylor Health Care System
Principal Investigator: Adam Mamelak, MD, Cedars-Sinai Medical Center
Principal Investigator: Steven Rosenfeld, MD, Columbia University
Principal Investigator: Jan Drappatz, MD, Dana-Farber Cancer Institute
Principal Investigator: Patrick Wen, MD, Dana-Farber Cancer Institute
Principal Investigator: Jeffrey Olson, MD, Emory University
Principal Investigator: Richard Wahl, MD, Johns Hopkins University
Principal Investigator: Heather Jacene, MD, Johns Hopkins University
Principal Investigator: Antonio Omuro, MD, Memorial Sloan Kettering Cancer Center
Principal Investigator: Edward Pan, MD, Moffitt Cancer Center
Principal Investigator: Sean Grimm, MD, Northwestern University
Principal Investigator: Jeffrey Raizer, MD, Northwestern University
Principal Investigator: Nimish Mobile, MD, University of Rochester
Principal Investigator: Marc Chamberlain, MD, University of Washington
Principal Investigator: Jay-Jiguang Zhu, MD, Tufts Medical Center
Principal Investigator: John Fiveash, MD, University of Alabama at Birmingham
Principal Investigator: David Schiff, MD, University of Virginia
Principal Investigator: Michael Edgeworth, MD, Vanderbilt University
Principal Investigator: Mark Malkin, MD, Medical College of Wisconsin
Principal Investigator: Maciej Mrugala, MD, University of Washington
Principal Investigator: Steven Chmura, MD, University of Chicago
Principal Investigator: Thomas Gribbin, MD, St. Mary's Health Care