GlioblastomaPhase 1NCT04200066
A Study of Maprotiline in Combination With Tamoxifen and Temozolomide for Recurrent Glioblastoma
A Phase 1 study testing Temozolomide, Tamoxifen, Maprotiline in people with Glioblastoma and Brain Tumor, run by University of Rochester.
Trial summary
The main purpose of this study is to find out the highest possible dose of maprotiline that can be given safely in combination with temozolomide and tamoxifen. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Brain Tumor
- What is being tested?
- Temozolomide, Tamoxifen, Maprotiline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2022to 1 Feb 2024
- 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 with histologically proven World Health Organization (WHO) grade IV gliomas. Patients will be eligible if the original histology was a grade II or grade III glioma as long as a subsequent histological diagnosis of a grade IV glioma is confirmed.
- Patients must have undergone upfront therapy that included a combination of radiotherapy and concurrent and adjuvant temozolomide.
- Patients must have shown unequivocal radiographic evidence for tumor progression by MRI scan. A scan should be performed within 10 days prior to registration and on a steroid dose that has been stable for at least five days. If the steroid dose is increased between the date of imaging and registration a new baseline MRI is required.
- Patients must have tissue confirmation of histology at the University of Rochester
- Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery (including gamma-knife or cyber-knife) must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium scanning, MR spectroscopy, MR Perfusion, or surgical documentation of disease. The decision of which modality to use to make this confirmation will be at the discretion of the investigator.
- Patients who have undergone re-resection for recurrent disease are eligible but must have an interval of 7 days prior to starting therapy.
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- All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information.
- Age > 18 years old, and with a life expectancy > eight weeks.
- Karnofsky Performance Status ≥ 70
- Patients must have an interval of at least 28 days from any investigational agent or from prior cytotoxic therapy, six weeks from prior nitrosureas, three weeks from procarbazine and two weeks from vincristine.
- Patients must have failed prior radiotherapy and must have an interval of greater than 90 days from completion of initial radiation therapy to study entry.
- WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 8 gm/dl). Patients must have adequate liver function (SGOT and bilirubin < 1.5 times ULN), and adequate renal function (creatinine clearance >30ml/min as measured by Cockroft-Gault formula) <before starting therapy. These tests must be performed within 2 weeks prior to treatment initiation. Eligibility level for hemoglobin may be reached by transfusion.
- Patients with any number of recurrences are eligible.
- Patients taking tamoxifen for other indications are eligible for the study
Who cannot join
- Patients who are within 3 months of treatment with radiation and concurrent temozolomide will not be eligible unless there are new enhancing abnormalities outside the high dose radiation fields (i.e. beyond the 80% isodose line) or surgical demonstration of active tumor.
- Patients must not be pregnant and must agree to practice adequate contraception. Women of childbearing potential must have a negative B-HCG pregnancy test documented within 7 days prior to registration. Women must not be breastfeeding.
- Patients with a history of other cancer (except non-melanoma skin cancer or cancer of the cervix), unless in complete remission for at least three years are ineligible.
- Concomitant use of enzyme inducing anti-epileptic drugs will be prohibited. These include phenytoin, phenobarbital, carbamazepine and oxacarbazepine. If patients are on these at time of study enrollment, drugs can be transitioned to a non-enzyme inducing anti-epileptic drug at the discretion of the investigator.
- Patients must not have any significant medical illnesses or other history that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
- Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.
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- Patients must not have concurrent use of other tricyclic antidepressants or MAO inhibitors.
- Patients with lower urinary tract symptoms secondary to benign prostatic hypertrophy that are refractory to medications
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
- Inability or unwillingness of subject or legal guardian/representative to give written informed consent.
- Patients with history of myocardial infarction within the past year.
- Patients with prior history of status epilepticus
- Patients with evidence of QTc prolongation greater than 450ms
- Patients receiving strong CYP2D6 inhibitors (bupropion, fluoxetine, paroxetine, quinidine, terbinafine) will be excluded.
- Patients receiving strong CYP3A4 inhibitors (Clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir) will be excluded.
- Patients with history of hypersensitivity to maprotiline.
- Patient meets the cut-off score of ≥ 12 in the PHQ-9 or selects a positive response of '1, 2, or 3' to question number 9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent of the total score of the PHQ-9)
About this study
Official title: A Phase 1 Study of Maprotiline in Combination With Tamoxifen and Temozolomide for Recurrent Glioblastoma
The main purpose of this study is to find out the highest possible dose of maprotiline that can be given safely in combination with temozolomide and tamoxifen.
Read the detailed description
The main purpose of this study is to find out the highest possible dose of maprotiline that can be given safely in combination with temozolomide and tamoxifen. Temozolomide is approved to treat glioblastoma and the investigator wants to understand what doses are safe to use. Tamoxifen has been used for many years to treat breast cancer and there have also been studies combining it with temozolomide for the treatment of brain tumors that have shown the combination to be safe. In this study, the investigator will be adding maprotiline to temozolomide and tamoxifen, determining the highest possible dose that is safe, making sure there are no significant drug interactions and studying the safety of this combination.
- Conditions
- Glioblastoma, Brain Tumor
- Being tested
- Temozolomide, Tamoxifen, Maprotiline
- Keywords
- Maprotiline, Tamoxifen, Temozolomide
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Temozolomide, Tamoxifen, MaprotilineDrug
Also called TMZ, TMX, TMT
Subjects will receive a combination of temozolomide and tamoxifen for two weeks. After that, they will receive a combination of temozolomide, tamoxifen and maprotiline for the remainder of the study. All drugs are administered orally. Subjects will undergo visits at the beginning of week 3, week 5 and week 7 that will involve multiple blood draws and ECGs to evaluate for pharmacokinetics and drug interactions. Response will be assessed every two months with an MRI and patients will continue on study as long as their tumors are under control and they are tolerating the regimen.
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | This arm will combine maprotiline with temozolomide and tamoxifen to determine the maximum tolerated dose. Receives: Drug: Temozolomide, Tamoxifen, Maprotiline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dosing Regimen (MTDR) of maprotiline in combination with temozolomide (TMZ) and tamoxifen (TMX)
Assessment of toxicity based on the NCI common toxicity criteria.
Measured: through study completion, an average of 6 months
Secondary outcomes (4)
Mean Maprotiline drug level
Blood sampling for pharmacokinetic assessment of study drugs. The mean maprotiline drug level will be reported. The drug levels will be measured at 2, 5, and 7 hours on weeks 1, 2, 3, 5 and 7
Measured: week 7
Median Maprotiline drug level
Blood sampling for pharmacokinetic assessment of study drugs. The median maprotiline drug level will be reported. The drug levels will be measured at 2, 5, and 7 hours on weeks 1, 2, 3, 5 and 7
Measured: week 7
6 mo Progression Free Survival
Measure of time from study enrollment until progression.
Progressive Disease: >25% increase in the bi-dimensional area OR an increase in T2/FLAIR abnormality that is consistent with tumor OR the presence of a new lesion OR clinical deterioration.
Measured: 6 months
Overall Survival
Measure of time from study enrollment until death from any cause.
Measured: from date of enrollment until date of death from any cause up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2019
- Study start1 Jun 2022 (estimated)
- Primary completion1 Oct 2023 (estimated)
- Study completion1 Feb 2024 (estimated)
Why it stopped: One of the drugs for the study is not commercially available.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by University of RochesterThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nimish Mohile, University of Rochester
- Investigators
- Nimish Mohile, MD, Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04200066
- Sponsor's protocol ID
- UBRT19062
- Status last verified
- Aug 2022
- First submitted
- 5 Dec 2019
- Last updated
- 22 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Maprotiline in Combination With Tamoxifen and Temozolomide for Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT04200066
- Acronym / sponsor ID
- UBRT19062
- Conditions
- Glioblastoma, Brain Tumor
- Keywords
- Maprotiline, Tamoxifen, Temozolomide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: One of the drugs for the study is not commercially available.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Study start
- 1 Jun 2022 (estimated)
- Primary completion
- 1 Oct 2023 (estimated)
- Study completion
- 1 Feb 2024 (estimated)
- First posted
- 16 Dec 2019 (actual)
- 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 main purpose of this study is to find out the highest possible dose of maprotiline that can be given safely in combination with temozolomide and tamoxifen.
Detailed description
The main purpose of this study is to find out the highest possible dose of maprotiline that can be given safely in combination with temozolomide and tamoxifen. Temozolomide is approved to treat glioblastoma and the investigator wants to understand what doses are safe to use. Tamoxifen has been used for many years to treat breast cancer and there have also been studies combining it with temozolomide for the treatment of brain tumors that have shown the combination to be safe. In this study, the investigator will be adding maprotiline to temozolomide and tamoxifen, determining the highest possible dose that is safe, making sure there are no significant drug interactions and studying the safety of this combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Drug: Temozolomide, Tamoxifen, MaprotilineThis arm will combine maprotiline with temozolomide and tamoxifen to determine the maximum tolerated dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients with histologically proven World Health Organization (WHO) grade IV gliomas. Patients will be eligible if the original histology was a grade II or grade III glioma as long as a subsequent histological diagnosis of a grade IV glioma is confirmed.
- Patients must have undergone upfront therapy that included a combination of radiotherapy and concurrent and adjuvant temozolomide.
- Patients must have shown unequivocal radiographic evidence for tumor progression by MRI scan. A scan should be performed within 10 days prior to registration and on a steroid dose that has been stable for at least five days. If the steroid dose is increased between the date of imaging and registration a new baseline MRI is required.
- Patients must have tissue confirmation of histology at the University of Rochester
- Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery (including gamma-knife or cyber-knife) must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium scanning, MR spectroscopy, MR Perfusion, or surgical documentation of disease. The decision of which modality to use to make this confirmation will be at the discretion of the investigator.
Key exclusion criteria (17 listed)
- Patients who are within 3 months of treatment with radiation and concurrent temozolomide will not be eligible unless there are new enhancing abnormalities outside the high dose radiation fields (i.e. beyond the 80% isodose line) or surgical demonstration of active tumor.
- Patients must not be pregnant and must agree to practice adequate contraception. Women of childbearing potential must have a negative B-HCG pregnancy test documented within 7 days prior to registration. Women must not be breastfeeding.
- Patients with a history of other cancer (except non-melanoma skin cancer or cancer of the cervix), unless in complete remission for at least three years are ineligible.
- Concomitant use of enzyme inducing anti-epileptic drugs will be prohibited. These include phenytoin, phenobarbital, carbamazepine and oxacarbazepine. If patients are on these at time of study enrollment, drugs can be transitioned to a non-enzyme inducing anti-epileptic drug at the discretion of the investigator.
- Patients must not have any significant medical illnesses or other history that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
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 |
|---|---|---|
| Temozolomide, Tamoxifen, MaprotilineAlso: TMZ, TMX, TMTSubjects will receive a combination of temozolomide and tamoxifen for two weeks. After that, they will receive a combination of temozolomide, tamoxifen and maprotiline for the remainder of the study. All drugs are administered orally. Subjects will undergo visits at the beginning of week 3, week 5 and week 7 that will involve multiple blood draws and ECGs to evaluate for pharmacokinetics and drug interactions. Response will be assessed every two months with an MRI and patients will continue on study as long as their tumors are under control and they are tolerating the regimen. | Drug | Experimental Arm |
Primary outcome
Maximum Tolerated Dosing Regimen (MTDR) of maprotiline in combination with temozolomide (TMZ) and tamoxifen (TMX)
Time frame: through study completion, an average of 6 months
Assessment of toxicity based on the NCI common toxicity criteria.
4 secondary outcomes
Mean Maprotiline drug level
Time frame: week 7
Median Maprotiline drug level
Time frame: week 7
6 mo Progression Free Survival
Time frame: 6 months
Overall Survival
Time frame: from date of enrollment until date of death from any cause up to 60 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2022.
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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.
Nimish Mohile, MD principal investigator
University of Rochester
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Temozolomide, Tamoxifen, Maprotiline in people with Glioblastoma and Brain Tumor, run by University of Rochester.
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 14 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: withdrawn, as of the sponsor's last update on 22 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Maximum Tolerated Dosing Regimen (MTDR) of maprotiline in combination with temozolomide (TMZ) and tamoxifen (TMX) (time frame: through study completion, an average of 6 months). 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 Aug 2022.