Tofacitinib for Glioblastoma

Recruiting in Palo Alto (17 mi)

Overseen by Michael Youssef, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: EGFR inhibitors, JAK inhibitors, Bevacizumab

Disqualifiers: Uncontrolled illness, Hypertension, Pregnancy, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests Tofacitinib, an oral medication, on patients with recurrent Glioblastoma. The drug works by reducing immune system activity, potentially slowing or stopping cancer growth. Tofacitinib is an oral medication initially used for the treatment of rheumatoid arthritis.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on Bevacizumab or any investigational agents for the cancer under study. If you have been on Bevacizumab, you must stop it for 180 days before joining the trial.

Is Tofacitinib generally safe for humans?

Tofacitinib, used for conditions like psoriatic arthritis and rheumatoid arthritis, has shown an acceptable safety profile in clinical trials, with low rates of serious infections, cancer, heart issues, and gut problems. Common side effects include infections and changes in blood tests, but it is generally well-tolerated in humans. ^{1 2 3 4 5}

How is the drug Tofacitinib different from other treatments for glioblastoma?

Tofacitinib is unique because it is a Janus kinase (JAK) inhibitor, which is a different mechanism of action compared to the standard treatments for glioblastoma like Temozolomide, which is a DNA-methylating agent, and bevacizumab, which targets vascular endothelial growth factor (VEGF). This novel approach may offer a new pathway for treating glioblastoma. ^{6 7 8 9 10}

Research Team

Michael Youssef, MD

Principal Investigator

Assistant Professor

Eligibility Criteria

Adults with recurrent Glioblastoma (GBM) who've had prior treatment, can swallow pills, and have a Karnofsky Performance Status of at least 60%. They must use contraception if of childbearing potential. Excluded are those with uncontrolled hypertension, other recent cancers, certain allergies or conditions that affect drug absorption or compliance.

Inclusion Criteria

I can care for myself but may need occasional help.

My brain tumor shows increased EGFR gene activity.

Patients must be willing and able to provide written informed consent and to comply with the study protocol as judged by the investigator.

Exclusion Criteria

I am allergic to medications similar to Tofacitinib.

Subjects must not be pregnant or nursing.

Patients unable to undergo brain MRI scans with IV gadolinium contrast.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tofacitinib 10 mg twice daily in 28-day cycles with assessments on Day 1 of each cycle

28 days per cycle

1 visit per cycle (in-person)

Interim Follow-up

Interim follow-up after the second cycle includes brain MRI for tumor measurements and other assessments

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including brain MRI and toxicity evaluations every 4 weeks

Up to 2 years

Treatment Details

Interventions

• Tofacitinib (Janus Kinase (JAK) Inhibitor)

Trial Overview The trial is testing the effects of Tofacitinib 10mg on patients with recurrent GBM. It aims to see how well this medication works for those whose tumors have EGFR gene amplification and who meet specific health criteria.

Participant Groups

Group I: Tofacitinib 10 mg Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Tofacitinib, an oral JAK inhibitor, demonstrated bioequivalence to Xeljanz® in a phase I trial involving 32 healthy Chinese subjects, with pharmacokinetic parameters such as peak concentration and area under the curve falling within the acceptable range of 80-125%.

The safety profile of tofacitinib was found to be comparable to that of Xeljanz®, supporting its potential for clinical use in treating inflammatory and autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, crossover, phase I clinical study to evaluate bioequivalence and safety of tofacitinib and Xeljanz® in Chinese healthy subjects. Xu, Z., Wang, Y., Liu, Z., et al.[2022]

Tofacitinib aspartate (7.13 mg) demonstrated bioequivalence to the reference formulation tofacitinib citrate (8.08 mg) in a study involving 41 healthy volunteers, indicating similar pharmacokinetic profiles for both formulations.

The study found that both formulations were well-tolerated, with no significant differences in maximum concentration (Cmax) and area under the concentration-time curve (AUClast), suggesting that tofacitinib aspartate can be a viable alternative to the existing formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence of the pharmacokinetics between tofacitinib aspartate and tofacitinib citrate in healthy subjects. Shin, W., Yang, AY., Yun, H., et al.[2022]

Tofacitinib, a pan Janus kinase inhibitor, has shown efficacy as a standalone treatment for patients new to methotrexate and those who did not respond fully to it, as well as in combination with other drugs for patients who failed TNF inhibitors, leading to its approval for use in many countries.

The clinical trials demonstrated a reasonable safety profile for tofacitinib, with ongoing assessments in long-term studies and postmarketing reports confirming its safety in diverse patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib in the treatment of active rheumatoid arthritis in adults. Fleischmann, R.[2018]

Tofacitinib (Xeljanz) is an effective treatment for rheumatoid arthritis (RA), showing comparable efficacy to adalimumab and improving disease control when used alone or with methotrexate.

While tofacitinib can reduce structural damage in RA, it carries risks of side effects such as upper respiratory infections and tuberculosis, necessitating careful monitoring of blood counts, lipids, and organ function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A new therapeutical option for chronic inflammation in rheumatology: janus kinases inhibitors (JAK)]. Varisco, PA., So, A.[2014]

Cilengitide, an integrin inhibitor, has shown promising antitumor activity against glioblastoma (GBM) in early clinical trials, with durable remissions reported in phase I and II studies.

Current research suggests that cilengitide may enhance the effectiveness of standard chemoradiotherapy for newly diagnosed GBM, and a pivotal phase III trial (CENTRIC) is underway to further evaluate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting integrins in malignant glioma. Tabatabai, G., Weller, M., Nabors, B., et al.[2021]

Temozolomide (TMZ) is a key treatment for glioblastomas, used after maximal safe tumor resection and radiation, but it has limited effectiveness with a 5-year survival rate of less than 10%.

Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, is being used for both initial and recurrent glioblastoma treatment, alongside BCNU wafers placed after surgery, indicating a multi-faceted approach to managing this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and Future Drug Treatments for Glioblastomas. Ohba, S., Hirose, Y.[2019]

In a phase II trial involving 57 patients with recurrent glioblastoma, gefitinib was found to be well tolerated, with mild adverse effects primarily consisting of skin reactions and diarrhea, and only 6% of patients withdrawing due to drug-related side effects.

Despite no objective tumor responses observed, gefitinib showed some activity with a 6-month event-free survival rate of 13% and a median overall survival of 39.4 weeks, suggesting potential benefits that warrant further investigation at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of gefitinib in recurrent glioblastoma. Rich, JN., Reardon, DA., Peery, T., et al.[2022]

Antiangiogenic therapy, which targets the blood vessel growth in glioblastoma multiforme (GBM), is being explored as a promising treatment option, with several agents like bevacizumab and aflibercept undergoing clinical trials.

The review highlights the biological rationale for targeting both VEGF and integrin pathways in GBM treatment, emphasizing the need to address the challenges in effectively applying these therapies in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contemporary Updates on Clinical Trials of Antiangiogenic Agents in the Treatment of Glioblastoma Multiforme. Kochar, AS., Madhavan, M., Manjila, S., et al.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Tofacitinib: A Review in Psoriatic Arthritis. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

A randomized, crossover, phase I clinical study to evaluate bioequivalence and safety of tofacitinib and Xeljanz® in Chinese healthy subjects. [2022]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Bioequivalence of the pharmacokinetics between tofacitinib aspartate and tofacitinib citrate in healthy subjects. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Tofacitinib in the treatment of active rheumatoid arthritis in adults. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

[A new therapeutical option for chronic inflammation in rheumatology: janus kinases inhibitors (JAK)]. [2014]

6. France pubmed.ncbi.nlm.nih.gov

Targeting integrins in malignant glioma. [2021]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Current and Future Drug Treatments for Glioblastomas. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Inhibition of elongation factor-2 kinase augments the antitumor activity of Temozolomide against glioma. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of gefitinib in recurrent glioblastoma. [2022]

10. India pubmed.ncbi.nlm.nih.gov

Contemporary Updates on Clinical Trials of Antiangiogenic Agents in the Treatment of Glioblastoma Multiforme. [2020]