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

NCT00683761 | Unknown Phase 1

• 1 other identifier: TM601-008
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 4

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.

Conditions

Malignant Glioma; Glioblastoma Multiforme; GBM; Astrocytoma; Oligodendroglioma

Keywords

High grade recurrent glioma; Phase 2; Phase 1; Multi-center; Open label; Multiple dose; Brain Cancer; Brain Tumor; GBM; glioma; glioblastoma; astrocytoma; oligodendroglioma; 131I-TM601; TM601

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• 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.

Study Arms (1)

1

EXPERIMENTAL

Drug: 131I-TM601

Interventions

131I-TM601 DRUG

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.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• TransMolecular: lead

Study Sites (4)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

St. Mary's Health Care

Grand Rapids, Michigan, 49503, United States

Location

University of Virginia

Charlottesville, Virginia, 22908-0394, United States

Location

Related Publications (4)

• Mamelak AN, Jacoby DB. Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601). Expert Opin Drug Deliv. 2007 Mar;4(2):175-86. doi: 10.1517/17425247.4.2.175.

  PMID: 17335414 BACKGROUND

• Mamelak AN, Rosenfeld S, Bucholz R, Raubitschek A, Nabors LB, Fiveash JB, Shen S, Khazaeli MB, Colcher D, Liu A, Osman M, Guthrie B, Schade-Bijur S, Hablitz DM, Alvarez VL, Gonda MA. Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma. J Clin Oncol. 2006 Aug 1;24(22):3644-50. doi: 10.1200/JCO.2005.05.4569.

  PMID: 16877732 BACKGROUND

• Hockaday DC, Shen S, Fiveash J, Raubitschek A, Colcher D, Liu A, Alvarez V, Mamelak AN. Imaging glioma extent with 131I-TM-601. J Nucl Med. 2005 Apr;46(4):580-6.

  PMID: 15809479 BACKGROUND

• Lyons SA, O'Neal J, Sontheimer H. Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin. Glia. 2002 Aug;39(2):162-73. doi: 10.1002/glia.10083.

  PMID: 12112367 BACKGROUND

MeSH Terms

Conditions

Glioma; Glioblastoma; Astrocytoma; Oligodendroglioma; Brain Neoplasms

Interventions

Chlorotoxin

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 21, 2008
• First Posted: May 23, 2008
• Study Start: August 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: April 1, 2010
• Last Updated: July 17, 2009

Record last verified: 2009-07

Locations

US (4)