Safety and Dose-Finding Study of TM-601 in Adults With Recurrent Malignant Glioma

NCT00591058 | Unknown Phase 1

• 1 other identifier: TM601-007
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to evaluate the safety and biologically active dose of TM-601 in adult patients with recurrent malignant glioma.

Conditions

Malignant Glioma; Glioblastoma Multiforme; GBM; Astrocytoma; Oligodendroglioma

Keywords

recurrent glioma; Phase I; Multi-Center; Open label; Brain Cancer; Brain tumor; GBM; Glioma; Glioblastoma multiforme

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (1)

• A primary objective of this study is to evaluate the biologically active dose of TM-601 in this population of patients based on changes in perfusion MRI parameters.

  At the completion of the dosing cycle for each patient, and at 28 days following the patient's final study treatment.

Study Arms (6)

Cohort 1

EXPERIMENTAL

0.04 mg/kg TM-601 dose per administration

Drug: TM-601

Cohort 2

EXPERIMENTAL

0.08 mg/kg TM-601 dose per administration

Drug: TM-601

Cohort 3

EXPERIMENTAL

0.16 mg/kg TM-601 dose per administration

Drug: TM-601

Cohort 4

EXPERIMENTAL

0.3 mg/kg TM-601 dose per administration

Drug: TM-601

Cohort 5

EXPERIMENTAL

0.6 mg/kg TM-601 dose per administration

Drug: TM-601

Cohort 6

EXPERIMENTAL

1.2 mg/kg TM-601 dose per administration

Drug: TM-601

Interventions

TM-601 DRUG

TM-601, administered intravenously (IV), once/week for 3 weeks

Also known as: Chlorotoxin (Synthetic)

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6

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 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.
• Be ≥18 years of age.
• Have a baseline Karnofsky Performance status of ≥60%
• Have a Mini Mental State Exam score ≥ 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 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
• Have a negative serum and urine 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 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.)
• 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.
• Be pregnant or breast-feeding.
• Have received radiation treatments ≤ 3 months from time of first study drug administration.
• Have received any cytotoxic chemotherapy, whether conventional or investigational, ≤ 4 weeks prior to enrollment 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-TM-601 e.g. iodine or iodine-containing drugs.

Sponsors & Collaborators

• TransMolecular: lead

Study Sites (7)

University of Alabama

Birmingham, Alabama, 35294-3410, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27157-1082, United States

Location

University of Washington

Seattle, Washington, 98195-6470, 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; Metabolism

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

• Burt Nabors, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Glenn Lesser, MD

  Wake Forest University

  PRINCIPAL INVESTIGATOR

• Steven Rosenfeld, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

• Sean Grimm, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

• Maceij Mrugala, MD

  University of Washington at Seattle

  PRINCIPAL INVESTIGATOR

• Jeremy Rudnick, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

• Gerry Linette, MD

  Washington University at St. Louis

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 27, 2007
• First Posted: January 11, 2008
• Study Start: February 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: July 17, 2009

Record last verified: 2009-07

Locations

US (7)