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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by TransMolecular.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
TransMolecular
ClinicalTrials.gov Identifier:
NCT00591058
First received: December 27, 2007
Last updated: July 16, 2009
Last verified: July 2009
  Purpose

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


Condition Intervention Phase
Malignant Glioma
Glioblastoma Multiforme
GBM
Astrocytoma
Oligodendroglioma
Drug: TM-601
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by TransMolecular:

Primary Outcome Measures:
  • 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. [ Time Frame: Throughout the treatment phase of the study for each study patient, and for 28 days following the final study dose. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. [ Time Frame: At the completion of the dosing cycle for each patient, and at 28 days following the patient's final study treatment. ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: February 2008
Estimated Study Completion Date: February 2010
Estimated Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
0.04 mg/kg TM-601 dose per administration
Drug: TM-601
TM-601, administered intravenously (IV), once/week for 3 weeks
Other Name: Chlorotoxin (Synthetic)
Experimental: Cohort 2
0.08 mg/kg TM-601 dose per administration
Drug: TM-601
TM-601, administered intravenously (IV), once/week for 3 weeks
Other Name: Chlorotoxin (Synthetic)
Experimental: Cohort 3
0.16 mg/kg TM-601 dose per administration
Drug: TM-601
TM-601, administered intravenously (IV), once/week for 3 weeks
Other Name: Chlorotoxin (Synthetic)
Experimental: Cohort 4
0.3 mg/kg TM-601 dose per administration
Drug: TM-601
TM-601, administered intravenously (IV), once/week for 3 weeks
Other Name: Chlorotoxin (Synthetic)
Experimental: Cohort 5
0.6 mg/kg TM-601 dose per administration
Drug: TM-601
TM-601, administered intravenously (IV), once/week for 3 weeks
Other Name: Chlorotoxin (Synthetic)
Experimental: Cohort 6
1.2 mg/kg TM-601 dose per administration
Drug: TM-601
TM-601, administered intravenously (IV), once/week for 3 weeks
Other Name: Chlorotoxin (Synthetic)

Detailed Description:

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 glioma.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 administration.
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00591058

Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294-3410
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, New York
Columbia University
New York, New York, United States, 10032
United States, North Carolina
Wake Forest University
Winston-Salem, North Carolina, United States, 27157-1082
United States, Washington
University of Washington
Seattle, Washington, United States, 98195-6470
Sponsors and Collaborators
TransMolecular
Investigators
Principal Investigator: Burt Nabors, MD University of Alabama at Birmingham
Principal Investigator: Glenn Lesser, MD Wake Forest School of Medicine
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
  More Information

Publications:
Responsible Party: TransMolecular, TransMolecular, Inc.
ClinicalTrials.gov Identifier: NCT00591058     History of Changes
Other Study ID Numbers: TM601-007
Study First Received: December 27, 2007
Last Updated: July 16, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by TransMolecular:
recurrent glioma
Phase I
Multi-Center
Open label
Brain Cancer
Brain tumor
GBM
Glioma
Glioblastoma multiforme

Additional relevant MeSH terms:
Glioblastoma
Glioma
Astrocytoma
Oligodendroglioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on October 16, 2014