Tofacitinib in Recurrent GBM Patients

NCT05326464 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: STU-2021-1029
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to examine the effects of Tofacitinib in patients with recurrent Glioblastoma.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 2 years after study treatment

Secondary Outcomes (3)

• Overall survival (OS) of the study cohort.

  Up to 2 years after study treatment

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability].

  Up to 2 years after study treatment

• Tumor response by RANO criteria.

  Up to 2 years after study treatment

Study Arms (1)

Tofacitinib 10 mg

EXPERIMENTAL

Participants will take the 10mg Tofacitinib twice daily until evidence of progression, intolerance of treatment, withdrawal of consent, or death.

Drug: Tofacitinib 10mg

Interventions

Tofacitinib 10mg DRUG

10 mg given orally twice daily until evidence of progression, intolerance of treatment, withdrawal of consent, or death.

Tofacitinib 10 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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:
• Surgery must have confirmed the recurrence.
• 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.
• 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:

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Pfizer: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Michael Youssef, MD

  Assistant Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ASSISTANT PROFESSOR - Neurology

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: April 13, 2022
• Study Start: October 7, 2022
• Primary Completion: June 16, 2025
• Study Completion (Estimated): June 1, 2027
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)