Malignant GliomaPhase 1/2NCT00683761
A Study of 131I-TM601 in Adults With Recurrent Malignant Glioma
A Phase 1/2 study testing 131I-TM601 in people with Malignant Glioma and Glioblastoma Multiforme, run by TransMolecular at 4 sites in United States.
Trial 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. 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?
- 131I-TM601
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 4 sitesUnited States
- Study dates
- Aug 2008to Apr 2010
- Phase
- Phase 1/2
- 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 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%.
Show all 17Show fewer
- 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.
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 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Johns Hopkins University
Baltimore, Maryland, 21287
University of Virginia
Charlottesville, Virginia, 22908-0394
University of Chicago
Chicago, Illinois, 60637
St. Mary's Health Care
Grand Rapids, Michigan, 49503
About this study
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
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.
Read the 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.
- Conditions
- Malignant Glioma, Glioblastoma Multiforme, GBM, Astrocytoma, Oligodendroglioma
- Being tested
- 131I-TM601
- 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
- 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.
131I-TM601Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: 131I-TM601 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Assessments timed within 3 days of study doses.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2008 (estimated)
- Study startAug 2008
- Primary completionFeb 2010 (estimated)
- Study completionApr 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TransMolecular
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Karen Fink, MD, Principal investigator, Baylor Health Care SystemAdam Mamelak, MD, Principal investigator, Cedars-Sinai Medical CenterSteven Rosenfeld, MD, Principal investigator, Columbia UniversityJan Drappatz, MD, Principal investigator, Dana-Farber Cancer InstitutePatrick Wen, MD, Principal investigator, Dana-Farber Cancer InstituteJeffrey Olson, MD, Principal investigator, Emory UniversityRichard Wahl, MD, Principal investigator, Johns Hopkins UniversityHeather Jacene, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00683761
- Sponsor's protocol ID
- TM601-008
- Status last verified
- Jul 2009
- First submitted
- 21 May 2008
- Last updated
- 17 Jul 2009
- Results posted
- No
- Data monitoring committee
- 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 1/2 Multi-Center, Safety and Efficacy Study Evaluating Intravenously Administered 131I-TM601 in Patients With Progressive and/or Recurrent Malignant Glioma
- ClinicalTrials.gov ID
- NCT00683761
- Acronym / sponsor ID
- TM601-008
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- TransMolecularIndustry (pharma, biotech, devices)
- Study start
- Aug 2008
- Primary completion
- Feb 2010 (estimated)
- Study completion
- Apr 2010 (estimated)
- First posted
- 23 May 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 effectiveness of 131I-TM601 in the treatment of adult patients with progressive or recurrent malignant gliomas.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: 131I-TM601 |
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 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%.
Key exclusion criteria (6 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 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.
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 |
|---|---|---|
| 131I-TM601In 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. | Drug | 1 |
Primary outcome
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.
Time frame: 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.
Time frame: At six months following first treatment dose, and until disease progression.
1 secondary outcome
Radiation absorbed dose to tumor and normal organs from IV administered 131I-TM601 in a subset of study patients.
Time frame: Assessments timed within 3 days of study doses.
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.
Karen Fink, MD principal investigator
Baylor Health Care System
Adam Mamelak, MD principal investigator
Cedars-Sinai Medical Center
Steven Rosenfeld, MD principal investigator
Columbia University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 131I-TM601 in people with Malignant Glioma and Glioblastoma Multiforme, run by TransMolecular at 4 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 6 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 4 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
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. (time frame: 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 study lists 2 primary outcomes in all. 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 NCT00683761, 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.