GlioblastomaPhase 3NCT05326464
Tofacitinib in Recurrent GBM Patients
A Phase 3 study testing Tofacitinib 10mg, Temozolomide and Lomustine in people with Glioblastoma, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to examine the effects of Tofacitinib in patients with recurrent Glioblastoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Tofacitinib 10mg, Temozolomide and Lomustine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Oct 2022to 31 Oct 2025
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histologically confirmed GBM (MGMT unmethylated, IDH wild type) at first, second, third, or fourth recurrence after concurrent chemoradiotherapy. Patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy determined the progressive tumor to be GBM.
- Imaging confirmation of first tumor progression or regrowth as defined by the Response Assessment in Neuro-Oncology (RANO) criteria. A minimum of 12 weeks must have elapsed from the completion of radiotherapy to study entry to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling.
- Karnofsky Performance Status (KPS) ≥ 60%.
- Patients must be willing and able to provide written informed consent and to comply with the study protocol as judged by the investigator.
- Age ≥ 18 years.
- Patients must be able to swallow oral medications.
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- For women who are of child-bearing potential and who are sexually active and who are not surgically sterile (absence of ovaries and/or uterus): to use an adequate method of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly) during the treatment period and for at least 6 months after last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. For male patients who are partners of premenopausal women: agreement to use a barrier method of contraception during the treatment period and for at least 6 months after the last dose of study drug.
- 7.1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- Patients who have undergone recent surgery for recurrent or progressive tumor are eligible provided that:
- 8.1 Surgery must have confirmed the recurrence.
- 8.2 A minimum of 28 days must have elapsed from the day of surgery to study entry. For core or needle biopsy, a minimum of 7 days must have elapsed prior to study entry.
- 8.3 Craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomization.
- Patients must have recovered (Common Terminology Criteria for Adverse Events CTCAE version 6] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. Minimum times from prior therapies include:
- 9.1 Greater than or equal to 28 days elapsed from the administration of any investigational agent.
- 9.2 Greater than or equal to 28 days elapsed from the administration of any prior cytotoxic agents, except ≥ 42 days from nitrosoureas. NOTE: Prior treatment with Novo-TTF therapy is allowed at initial diagnosis but must be discontinued prior to study entry.
- GBMs of the study patients must have EGFR gene amplification, which will be detected by next generation sequencing of tumor tissue from resected sample.
- Prior use of bevacizumab is allowed, however patient must be off of this medication for 180 days.
- Patients must have adequate organ and marrow function as defined by the following criteria:
- ANC ≥1.5 × 10(9)/L
- Platelets ≥100 × 10(9)/L
- Hemoglobin ≥8 g/dL
- Total bilirubin ≤1.5 × ULN Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
- ALT and AST ≤3 × ULN
Who cannot join
- Prior treatment with an EGFR or JAK inhibitor.
- Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
- Patients unable to undergo brain MRI scans with IV gadolinium contrast.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Tofacitinib
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
- Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
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- Prior history of hypertensive crisis, hypertensive encephalopathy, or inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg while on antihypertensive medication).
- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant gastrointestinal resection that would preclude adequate absorption of the trial medications.
- History of another malignancy in the previous 3 years, with a disease-free interval of < 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
- Concurrent use of Bevacizumab.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
About this study
Official title: Tofacitinib: Suppressing Tumor Invasion in Recurrent GBM Patients
The purpose of this study is to examine the effects of Tofacitinib in patients with recurrent Glioblastoma.
Read the detailed description
Once consented and registered, eligible patients will commence Cycle 1 and be assessed on Cycle 1 Day 1. An entire cycle will be 28 days of continuous Tofacitinib dosing. There will be a gap of 18-24 days between the first and subsequent cycles of treatment. The patient will once again be assessed on Cycle 2 Day 1. An interim follow-up will be done after the second cycle, during which the patient will undergo a brain MRI for tumor measurements along with all other assessments. Subsequent cycles will continue as prior, with subject assessments, brain MRI, and toxicity evaluations every 4 weeks. Treatments will stop upon evidence of disease progression, unacceptable toxicity, or if the physician deems it unsafe for the subject to continue in the study.
- Conditions
- Glioblastoma
- Being tested
- Tofacitinib 10mg, Temozolomide, Lomustine
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tofacitinib 10mgDrug
10 mg given orally twice daily until evidence of progression, intolerance of treatment, withdrawal of consent, or death.
TemozolomideDrug
Temozolomide 150mg/m2 - 200mg/m2 on days 1-5
LomustineDrug
Lomustine 90mg/m2 on day 1
| Study group | Role | What they receive |
|---|---|---|
| Newly diagnosed or Recurrent off Temozolomide | Experimental | Participants will take Tofacitinib 10mg BID x 28 days with Temozolomide 150mg/m2 on days 1-5. Receives: Drug: Tofacitinib 10mg; Drug: Temozolomide |
| Recurrent disease on Temozolomide | Experimental | Tofacitinib 10mg BID x 42 days Lomustine 90mg/m2 Receives: Drug: Tofacitinib 10mg; Drug: Lomustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) of the Study Cohort as Defined by RANO Criteria.
Median progression-free survival from initiation of Tofacitinib until disease progression as defined by the RANO criteria, unacceptable toxicity, withdrawal of consent, or discontinuation from the trial for any other reason.
Measured: From treatment initiation until documented radiographic or clinical progression by RANO criteria or death, whichever came first, assessed up to 2 years.
Secondary outcomes (3)
Overall Survival (OS) of the Study Cohort.
Median OS of the study patients from time of study entry until death or lost to follow-up.
Measured: From treatment initiation until documented radiographic or clinical progression by RANO criteria or death, whichever came first, assessed up to 2 years.
Percentage of Treatment Related Adverse Events
Assess safety and tolerability associated with Tofacitinib 5 mg orally twice daily when administered to GBM patients. NCI Common terminology criteria for adverse events (CTCAE v.5) will be used to assess the adverse events.
Measured: Up to 2 years after completion of study treatment, an average of 34 months
Radiographic Response Rate by RANO Criteria (Number of Participants With Response)
Tumor response will be assessed using contrast and non-contrast brain magnetic resonance imaging (MRI) with assessments based on the international criteria proposed by the Response Assessment in Neuro-Oncology (RANO) Working Group, until progression of disease. For patients who do not progress or die, PFS will be censored at the last adequate radiologic assessment.
RANO criteria:
Complete Response (CR): Complete disappearance of all enhancing measurable and non measurable disease sustained for at least 4 weeks; Partial Response (PR): ≥50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; Progressive Disease (PD): ≥25% increase in the sum of products of perpendicular diameters of enhancing lesions compared to the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids;
Measured: From treatment initiation until documented radiographic response by RANO criteria or death, whichever came first, assessed up to 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2022
- Study start7 Oct 2022
- Primary completion18 Feb 2025
- Study completion31 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GlioblastomaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Michael Youssef, University of Texas Southwestern Medical Center
- Investigators
- Michael Youssef, MD, Principal investigator, Assistant Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05326464
- Sponsor's protocol ID
- STU-2021-1029
- Status last verified
- Jun 2026
- First submitted
- 5 Apr 2022
- Last updated
- 29 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tofacitinib: Suppressing Tumor Invasion in Recurrent GBM Patients
- ClinicalTrials.gov ID
- NCT05326464
- Acronym / sponsor ID
- STU-2021-1029
- Conditions
- Glioblastoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 7 Oct 2022 (actual)
- Primary completion
- 18 Feb 2025 (actual)
- Study completion
- 31 Oct 2025 (actual)
- First posted
- 13 Apr 2022 (actual)
- Results
- Posted 29 Jun 2026
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 examine the effects of Tofacitinib in patients with recurrent Glioblastoma.
Detailed description
Once consented and registered, eligible patients will commence Cycle 1 and be assessed on Cycle 1 Day 1. An entire cycle will be 28 days of continuous Tofacitinib dosing. There will be a gap of 18-24 days between the first and subsequent cycles of treatment. The patient will once again be assessed on Cycle 2 Day 1. An interim follow-up will be done after the second cycle, during which the patient will undergo a brain MRI for tumor measurements along with all other assessments. Subsequent cycles will continue as prior, with subject assessments, brain MRI, and toxicity evaluations every 4 weeks. Treatments will stop upon evidence of disease progression, unacceptable toxicity, or if the physician deems it unsafe for the subject to continue in the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Newly diagnosed or Recurrent off Temozolomide | Experimental | Drug: Tofacitinib 10mg, Drug: TemozolomideParticipants will take Tofacitinib 10mg BID x 28 days with Temozolomide 150mg/m2 on days 1-5. |
| Recurrent disease on Temozolomide | Experimental | Drug: Tofacitinib 10mg, Drug: LomustineTofacitinib 10mg BID x 42 days Lomustine 90mg/m2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Histologically confirmed GBM (MGMT unmethylated, IDH wild type) at first, second, third, or fourth recurrence after concurrent chemoradiotherapy. Patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy determined the progressive tumor to be GBM.
- Imaging confirmation of first tumor progression or regrowth as defined by the Response Assessment in Neuro-Oncology (RANO) criteria. A minimum of 12 weeks must have elapsed from the completion of radiotherapy to study entry to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling.
- Karnofsky Performance Status (KPS) ≥ 60%.
- Patients must be willing and able to provide written informed consent and to comply with the study protocol as judged by the investigator.
- Age ≥ 18 years.
Key exclusion criteria (10 listed)
- Prior treatment with an EGFR or JAK inhibitor.
- Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
- Patients unable to undergo brain MRI scans with IV gadolinium contrast.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Tofacitinib
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
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 |
|---|---|---|
| Tofacitinib 10mg10 mg given orally twice daily until evidence of progression, intolerance of treatment, withdrawal of consent, or death. | Drug | Newly diagnosed or Recurrent off Temozolomide, Recurrent disease on Temozolomide |
| TemozolomideTemozolomide 150mg/m2 - 200mg/m2 on days 1-5 | Drug | Newly diagnosed or Recurrent off Temozolomide |
| LomustineLomustine 90mg/m2 on day 1 | Drug | Recurrent disease on Temozolomide |
Primary outcome
Progression-free Survival (PFS) of the Study Cohort as Defined by RANO Criteria.
Time frame: From treatment initiation until documented radiographic or clinical progression by RANO criteria or death, whichever came first, assessed up to 2 years.
Median progression-free survival from initiation of Tofacitinib until disease progression as defined by the RANO criteria, unacceptable toxicity, withdrawal of consent, or discontinuation from the trial for any other reason.
3 secondary outcomes
Overall Survival (OS) of the Study Cohort.
Time frame: From treatment initiation until documented radiographic or clinical progression by RANO criteria or death, whichever came first, assessed up to 2 years.
Percentage of Treatment Related Adverse Events
Time frame: Up to 2 years after completion of study treatment, an average of 34 months
Radiographic Response Rate by RANO Criteria (Number of Participants With Response)
Time frame: From treatment initiation until documented radiographic response by RANO criteria or death, whichever came first, assessed up to 2 years.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Michael Youssef, MD principal investigator
Assistant Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tofacitinib 10mg, Temozolomide and Lomustine in people with Glioblastoma, run by University of Texas Southwestern Medical Center at 1 site 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 25 inclusion and 10 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: finished, as of the sponsor's last update on 29 Jun 2026. 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 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression-free Survival (PFS) of the Study Cohort as Defined by RANO Criteria. (time frame: From treatment initiation until documented radiographic or clinical progression by RANO criteria or death, whichever came first, assessed up to 2 years.). 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 29 Jun 2026.