Malignant GliomaPhase 1NCT00591058
Safety and Dose-Finding Study of TM-601 in Adults With Recurrent Malignant Glioma
A Phase 1 study testing TM-601 in people with Malignant Glioma and Glioblastoma Multiforme, run by TransMolecular at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Glioma, Glioblastoma Multiforme, GBM
- What is being tested?
- TM-601
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 7 sitesUnited States
- Study dates
- Feb 2008to Feb 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 17Show fewer
- 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.
- Have signed and dated written informed consent.
- Be able to comply with treatment plan, study procedures and follow-up examinations.
Who cannot join
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Alabama
Birmingham, Alabama, 35294-3410
Northwestern University
Chicago, Illinois, 60611
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Columbia University
New York, New York, 10032
University of Washington
Seattle, Washington, 98195-6470
Washington University
St Louis, Missouri, 63110
Wake Forest University
Winston-Salem, North Carolina, 27157-1082
About this study
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
The purpose of this study is to evaluate the safety and biologically active dose of TM-601 in adult patients with recurrent malignant glioma.
Read the 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.
- Conditions
- Malignant Glioma, Glioblastoma Multiforme, GBM, Astrocytoma, Oligodendroglioma
- Being tested
- TM-601
- Keywords
- recurrent glioma, Phase I, Multi-Center, Open label, Brain Cancer, Brain tumor, GBM, Glioma, Glioblastoma multiforme
- Medical subject headings
- Glioma, Glioblastoma, Astrocytoma, Oligodendroglioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TM-601Drug
Also called Chlorotoxin (Synthetic)
TM-601, administered intravenously (IV), once/week for 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 0.04 mg/kg TM-601 dose per administration Receives: Drug: TM-601 |
| Cohort 2 | Experimental | 0.08 mg/kg TM-601 dose per administration Receives: Drug: TM-601 |
| Cohort 3 | Experimental | 0.16 mg/kg TM-601 dose per administration Receives: Drug: TM-601 |
| Cohort 4 | Experimental | 0.3 mg/kg TM-601 dose per administration Receives: Drug: TM-601 |
| Cohort 5 | Experimental | 0.6 mg/kg TM-601 dose per administration Receives: Drug: TM-601 |
| Cohort 6 | Experimental | 1.2 mg/kg TM-601 dose per administration Receives: Drug: TM-601 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: At the completion of the dosing cycle for each patient, and at 28 days following the patient's final study treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2008 (estimated)
- Study startFeb 2008
- Primary completionFeb 2010 (estimated)
- Study completionFeb 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Malignant GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TransMolecular
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Burt Nabors, MD, Principal investigator, University of Alabama at BirminghamGlenn Lesser, MD, Principal investigator, Wake Forest UniversitySteven Rosenfeld, MD, PhD, Principal investigator, Columbia UniversitySean Grimm, MD, Principal investigator, Northwestern UniversityMaceij Mrugala, MD, Principal investigator, University of Washington at SeattleJeremy Rudnick, MD, Principal investigator, Cedars-Sinai Medical CenterGerry Linette, MD, Principal investigator, Washington University at St. Louis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00591058
- Sponsor's protocol ID
- TM601-007
- Status last verified
- Jul 2009
- First submitted
- 27 Dec 2007
- Last updated
- 17 Jul 2009
- Results posted
- No
Publications
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.
PubMed 17335414Mamelak 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.
PubMed 16877732Hockaday 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.
PubMed 15809479Lyons 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.
PubMed 12112367
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00591058
- Acronym / sponsor ID
- TM601-007
- Conditions
- Malignant Glioma, Glioblastoma Multiforme, GBM, Astrocytoma, Oligodendroglioma
- Keywords
- recurrent glioma, Phase I, Multi-Center, Open label, Brain Cancer, Brain tumor, GBM, Glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- TransMolecularIndustry (pharma, biotech, devices)
- Study start
- Feb 2008
- Primary completion
- Feb 2010 (estimated)
- Study completion
- Feb 2010 (estimated)
- First posted
- 11 Jan 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and biologically active dose of TM-601 in adult patients with recurrent malignant glioma.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: TM-6010.04 mg/kg TM-601 dose per administration |
| Cohort 2 | Experimental | Drug: TM-6010.08 mg/kg TM-601 dose per administration |
| Cohort 3 | Experimental | Drug: TM-6010.16 mg/kg TM-601 dose per administration |
| Cohort 4 | Experimental | Drug: TM-6010.3 mg/kg TM-601 dose per administration |
| Cohort 5 | Experimental | Drug: TM-6010.6 mg/kg TM-601 dose per administration |
| Cohort 6 | Experimental | Drug: TM-6011.2 mg/kg TM-601 dose per administration |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (7 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TM-601Also: Chlorotoxin (Synthetic)TM-601, administered intravenously (IV), once/week for 3 weeks | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6 |
Primary outcome
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.
1 secondary outcome
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2009.
- Background: PubMed 17335414Mamelak 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.
- Background: PubMed 16877732Mamelak 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.
- Background: PubMed 15809479Hockaday 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.
- Background: PubMed 12112367Lyons 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Burt Nabors, MD principal investigator
University of Alabama at Birmingham
Glenn Lesser, MD principal investigator
Wake Forest University
Steven Rosenfeld, MD, PhD principal investigator
Columbia University
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TM-601 in people with Malignant Glioma and Glioblastoma Multiforme, run by TransMolecular at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Jul 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00591058, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2009.