Glioblastoma Multiforme (GBM)Phase 2NCT02654041
Study of Induction of Hypothyroxinemia Adjunct to Conventional Therapies in GBM Patients
A Phase 2 study testing Combined T3 and Methimazole treatment in people with Glioblastoma Multiforme (GBM), run by Musli Thyropeutics Ltd. at 1 site in Israel.
Trial summary
The objective of the study is to assess the safety and efficacy of treatment with hypothyroxinemia adjunct to conventional therapies in GBM patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme (GBM)
- What is being tested?
- Combined T3 and Methimazole treatment
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteIsrael
- Study dates
- Mar 2016to Jun 2017
- Phase
- Phase 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
- Diagnosis of GBM, histologically or cytologically confirmed.
- Newly-diagnosed subjects prior to beginning first-line conventional therapy.
- Male or female subjects 18 years of age or older.
- Ability to understand and willingness to sign a written informed consent document.
- Ability and consent to comply with completion of a patient diary.
- Subjects must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) with conventional techniques or as ≥10 mm (≥1 cm) with spiral CT scan, MRI, or calipers by clinical exam.
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- Allowable type and amount of prior therapy and medication
- ECOG performance status ≤2 (KPS ≥60%, see Appendix A).
- Life expectancy of greater than 6 months
- Subjects must have adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting to study treatment:
- Total bilirubin < 1.5 x the upper limit of normal (ULN).
- Alanine transaminase (ALT) and aspartate aminotransferase (AST) < 2.5 xULN (< 5 x ULN for subjects with liver involvement of their cancer).
- Alkaline phosphatase limit < 2.5 x ULN (<5 x ULN for subjects with liver involvement of their cancer)
- Serum creatinine < 1.5 x the ULN. Glomerular filtration rate (GFR) ≥ 30 ml/min/1.73 m2 according to the MDRD (Modified diet in renal disease) abbreviated formula.
- INR/PTT < 1.5 x ULN.
- Platelet count > 100000 /mm3, Hemoglobin (Hb) > 9 g/dl, Absolute neutrophil count (ANC) > 1500/mm3
- No significant abnormalities in serum hematology, serum chemistry and serum inflammatory / immunogenic markers according to the Principal Investigator's judgment.
- No significant abnormalities in urinalysis according to the Principal Investigator's judgment, taking into considerations the potential effects of the tumor.
- No significant abnormalities in ECG per investigator judgment.
- Non-pregnant, non-lactating female subjects.
- Women of childbearing potential and men must agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study.
Who cannot join
- Patients unable to swallow oral medications.
- Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication.
- Patients who are receiving any other investigational agents or participating in another interventional clinical trial within 30 days prior to baseline visit (patients participating in other observational trials are allowed to be enrolled in this study).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to anti-thyroid agent (such as methimazole or PTU) or Cytomel®, or other agents used in study.
- Current or prior (within the last 60 days prior to screening visit) use of any medication or substance that have the potential to affect the activity or pharmacokinetics of the study agents (please refer to package inserts of study drugs).
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- Specific none-allowable type and amount of prior therapy and medication
- Clinically significant concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active connective tissue disorders, such as lupus or scleroderma, human immunodeficiency virus or psychiatric illness/social situations that in the opinion of the investigator, could interfere with the safety, compliance or other aspects of this study and would limit compliance with study requirements.
- History of organ allograft.
- Non-healing wound, ulcer, or bone fracture.
- Renal failure requiring hemo-or peritoneal dialysis.
- Pregnant or breast-feeding patients. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment.
- Evidence of uncontrolled hypertension (systolic blood pressure of >150 mm Hg, and/or diastolic blood pressure of >100 mm Hg) (at any time) when taken 3 times on the same arm with the subject in the supine position.
- Evidence of alcohol abuse or history of alcohol abuse or illegal and/or legally prescribed drugs.
- Inability to attend scheduled clinic visits and/or comply with the study protocol.
- Any other factor that, in the opinion of the investigator, would prevent the patient from complying with the requirements of the protocol.
- Any prior abnormalities related to the thyroid and /or intake of thyroid related drugs (e.g Eltroxin) in the 3 months prior to the study start.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II, Open-label, Prospective, Single-arm, Single-center Study of Induction of Hypothyroxinemia Adjunct to Conventional Therapies in GBM Patients
The objective of the study is to assess the safety and efficacy of treatment with hypothyroxinemia adjunct to conventional therapies in GBM patients.
Read the detailed description
Since T4 (thyroxine) is a potent growth factor in numerous cancer types, the interventional approach will be to achieve thyroxine deprivation (hypothyroxinemia).This can be achieved by using a dual approach: T3 and methimazole to provide longer term inhibition of thyroid hormone synthesis.
- Conditions
- Glioblastoma Multiforme (GBM)
- Being tested
- Combined T3 and Methimazole treatment
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combined T3 and Methimazole treatmentDrug
Oral administration of T3 and Methimazole
| Study group | Role | What they receive |
|---|---|---|
| Hypothyroxinemia induced patients | Experimental | Combined T3 and Methimazole treatment will be administered. This experimental treatment will be administered adjunct to standard oncological treatment for newly-diagnosed GBM patients e.g. radiation followed by Temozolomide. Receives: Drug: Combined T3 and Methimazole treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate at 6 months (6 months PFS)
The primary outcome measure of the study is the ratio of patients who complete their 6-month course of chemotherapy given the IP adjunct treatment. Each patient is treated up to 6 weeks until their FT4 target is reached at which time they enter a 26 week (6 month) treatment phase during which they receive chemotherapy as per common protocol with the IP as adjunct treatment. Patients will be monitored for disease progression as per common oncological protocol (e.g. every 2 months) and those who show progression will be deemed failures. Patients with no disease progression (or partial or complete remission) at the end of the 6 month period will be considered success.
Measured: 32 weeks
Secondary outcomes (4)
Response rate at 2 months (2 months PFS)
As a secondary outcome we will measure 2 month progression free survival as measured by RANO.
Measured: 14 weeks
Response rate at 4 months (4 months PFS)
As a secondary outcome we will measure 4 month progression free survival as measured by RANO.
Measured: 23 weeks
Time to disease progression or cancer-related death
Measured: 32 weeks
Safety endpoint evaluation
Patients will be monitored throughout the study period for any Hypothyroxinemia treatment related safety issues including serious adverse events, any adverse events, vital signs, lab assessment, physical examination and lung function.
Measured: 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2016 (estimated)
- Study startMar 2016
- Primary completionJun 2017
- Study completionJun 2017
Why it stopped: Drug manufacturer no longer could supply for study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma Multiforme (GBM)Studies 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 2
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Musli Thyropeutics Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Tel-Aviv Sourasky Medical Center
- Responsible party
- Sponsor
- Investigators
- Deborah T Blumenthal, MD, Principal investigator, Tel-Aviv Medical Center, Israel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02654041
- Sponsor's protocol ID
- MusliGBM002
- Status last verified
- Nov 2016
- First submitted
- 11 Jan 2016
- Last updated
- 22 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II, Open-label, Prospective, Single-arm, Single-center Study of Induction of Hypothyroxinemia Adjunct to Conventional Therapies in GBM Patients
- ClinicalTrials.gov ID
- NCT02654041
- Acronym / sponsor ID
- MusliGBM002
- Conditions
- Glioblastoma Multiforme (GBM)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Drug manufacturer no longer could supply for study
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Musli Thyropeutics Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Tel-Aviv Sourasky Medical Center
- Study start
- Mar 2016
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 13 Jan 2016 (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 objective of the study is to assess the safety and efficacy of treatment with hypothyroxinemia adjunct to conventional therapies in GBM patients.
Detailed description
Since T4 (thyroxine) is a potent growth factor in numerous cancer types, the interventional approach will be to achieve thyroxine deprivation (hypothyroxinemia).This can be achieved by using a dual approach: T3 and methimazole to provide longer term inhibition of thyroid hormone synthesis.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hypothyroxinemia induced patients | Experimental | Drug: Combined T3 and Methimazole treatmentCombined T3 and Methimazole treatment will be administered. This experimental treatment will be administered adjunct to standard oncological treatment for newly-diagnosed GBM patients e.g. radiation followed by Temozolomide. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Diagnosis of GBM, histologically or cytologically confirmed.
- Newly-diagnosed subjects prior to beginning first-line conventional therapy.
- Male or female subjects 18 years of age or older.
- Ability to understand and willingness to sign a written informed consent document.
- Ability and consent to comply with completion of a patient diary.
Key exclusion criteria (17 listed)
- Patients unable to swallow oral medications.
- Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication.
- Patients who are receiving any other investigational agents or participating in another interventional clinical trial within 30 days prior to baseline visit (patients participating in other observational trials are allowed to be enrolled in this study).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to anti-thyroid agent (such as methimazole or PTU) or Cytomel®, or other agents used in study.
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 |
|---|---|---|
| Combined T3 and Methimazole treatmentOral administration of T3 and Methimazole | Drug | Hypothyroxinemia induced patients |
Primary outcome
Response rate at 6 months (6 months PFS)
Time frame: 32 weeks
The primary outcome measure of the study is the ratio of patients who complete their 6-month course of chemotherapy given the IP adjunct treatment. Each patient is treated up to 6 weeks until their FT4 target is reached at which time they enter a 26 week (6 month) treatment phase during which they receive chemotherapy as per common protocol with the IP as adjunct treatment. Patients will be monitored for disease progression as per common oncological protocol (e.g. every 2 months) and those who show progression will be deemed failures. Patients with no disease progression (or partial or complete remission) at the end of the 6 month period will be considered success.
4 secondary outcomes
Response rate at 2 months (2 months PFS)
Time frame: 14 weeks
Response rate at 4 months (4 months PFS)
Time frame: 23 weeks
Time to disease progression or cancer-related death
Time frame: 32 weeks
Safety endpoint evaluation
Time frame: 32 weeks
Results and safety
The study was stopped early (reason given: Drug manufacturer no longer could supply for study). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2018.
- Individual participant dataSharing planned: Undecided
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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.
Deborah T Blumenthal, MD principal investigator
Tel-Aviv Medical Center, Israel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Combined T3 and Methimazole treatment in people with Glioblastoma Multiforme (GBM), run by Musli Thyropeutics Ltd. at 1 site in Israel.
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 21 inclusion and 17 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: stopped early, as of the sponsor's last update on 22 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. 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 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?
The study was stopped early (reason given: Drug manufacturer no longer could supply for 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?
Response rate at 6 months (6 months PFS) (time frame: 32 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Mar 2018.