Mycophenolate Mofetil + Standard Care for Glioblastoma

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Northwestern University

Must not be taking: Investigational agents, Viral-vector therapy

Disqualifiers: Uncontrolled epilepsy, Concurrent malignancy, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 36

Duration: 24 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for glioblastoma, a type of brain cancer. Researchers aim to determine if adding mycophenolate mofetil, an immunosuppressant drug, to the usual cancer treatments (temozolomide and possibly radiation therapy) can prevent cancer growth. The trial will assess the safety of this combination and any potential side effects. Individuals with glioblastoma who have already undergone surgery or a biopsy might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are on other investigational drugs or require live vaccinations within two weeks of starting the trial medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that mycophenolate mofetil (MMF), when combined with temozolomide and radiation therapy, has been studied for safety in treating glioblastoma, a type of brain cancer. Studies have found that MMF can reach both active and less-active parts of the tumor and block a crucial process that tumors need to grow, suggesting its potential effectiveness in targeting tumor cells.

MMF is generally used to prevent organ rejection in transplant patients, providing some information about its safety. However, since this trial is in its early stages, it primarily focuses on assessing safety, side effects, and determining the best dose. While evidence of MMF's safety exists in other contexts, its safety in this specific combination and setting remains under evaluation. Participants might experience side effects, and the trial aims to identify and manage these effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for glioblastoma because they introduce mycophenolate mofetil (MMF) alongside established options like temozolomide (TMZ) and radiation therapy. Unlike standard treatments, which typically focus on TMZ and radiation alone, MMF adds a new dimension by potentially enhancing the immune system's ability to fight the tumor. This combination aims to increase the effectiveness of existing therapies, offering hope for better outcomes by targeting the cancer more comprehensively. By integrating MMF, researchers hope to improve the standard care for glioblastoma, making it a promising advancement in the treatment landscape.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

Research has shown that the drug temozolomide (TMZ) effectively treats glioblastoma, a type of brain cancer. Studies have found that combining TMZ with radiation therapy extends survival. For example, one study reported that 70% of patients survived for 10 years with the combined treatment, compared to 47% with radiation alone. Radiation therapy alone also plays a crucial role in managing glioblastoma and offers survival benefits. In this trial, some participants will receive TMZ and radiation therapy, while others will receive TMZ and mycophenolate mofetil (MMF). MMF, typically used to prevent organ rejection, might help make tumor cells more responsive to chemotherapy like TMZ. Researchers are still studying MMF's effectiveness for glioblastoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Priya U. Kumthekar

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

Adults diagnosed with glioblastoma, who've had surgery or biopsy and are stable on low-dose corticosteroids. They must be able to perform daily activities (Karnofsky score >=70), have adequate organ function, and agree to use contraception. Excluded are those with other cancers, certain infections, uncontrolled illnesses, pregnant/nursing women, inability to take oral meds, or known HIV/HBV/HCV.

Inclusion Criteria

Patients with specific laboratory values within 14 days prior to study registration

My brain tumor is confirmed as glioblastoma or has similar features.

My dose of corticosteroids is stable or decreasing.

Exclusion Criteria

I do not have uncontrolled epilepsy, another cancer needing treatment, severe infections, immune issues, major psychiatric illness, and I'm not pregnant or nursing. I also don't have trouble swallowing or a history of HIV, HBV, or HCV.

I do not have another cancer that could affect this study's treatment or safety.

Patients with history of allergic reactions to compounds similar to temozolomide or mycophenolate mofetil

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive mycophenolate mofetil (MMF) in combination with temozolomide (TMZ) and/or radiation therapy. Treatment repeats every 28 days for up to 6 cycles.

24 weeks

Daily visits for radiation therapy during the first 6 weeks, followed by regular visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Follow-up at 30 days post-treatment, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Mycophenolate Mofetil
• Radiation Therapy
• Temozolomide

Trial Overview The trial is testing the safety and optimal dose of Mycophenolate Mofetil when combined with standard treatments for glioblastoma: Temozolomide and Radiation Therapy. The goal is to see if this drug makes cancer cells more sensitive to treatment.

How Is the Trial Designed?

Group I: Group S (pre-surgical MMF, TMZ) Experimental Treatment 3 Interventions

Patients planning to undergo surgery receive MMF PO BID and TMZ PO QD for 5 days prior to surgery in the absence of disease progression or unacceptable toxicity.

Group II: Group 3 (TMZ, MMF, radiation therapy) Experimental Treatment 4 Interventions

Patients who have already undergone surgery or biopsy receive TMZ PO QD on days 1-5 of each cycle and MMF PO BID. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Starting at the same time as TMZ and MMF administration, patients also receive radiation therapy daily, 5 days per week, for 6 weeks.

Group III: Group 2 (TMZ, MMF, radiation therapy) Experimental Treatment 4 Interventions

Patients with unmethylated glioblastoma who have already undergone surgery or biopsy receive TMZ PO QD on days 1-5 of each cycle and MMF PO BID. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Starting at the same time as TMZ and MMF administration, patients also receive radiation therapy daily, 5 days per week, for 6 weeks.

Group IV: Group 1 (TMZ, MMF) Experimental Treatment 3 Interventions

Patients who have already undergone surgery or biopsy followed by chemoradiation receive TMZ PO QD on days 1-5 of each cycle and MMF PO BID. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Mycophenolate Mofetil is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cellcept for:

• Prevention of acute organ rejection in kidney, liver, and heart transplant patients
• Treatment of autoimmune diseases such as lupus nephritis and rheumatoid arthritis

Approved in United States as Cellcept for:

• Prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac, or hepatic transplants
• Treatment of autoimmune diseases such as lupus nephritis and rheumatoid arthritis

Approved in Canada as Cellcept for:

• Prevention of acute organ rejection in kidney, liver, and heart transplant patients
• Treatment of autoimmune diseases such as lupus nephritis and rheumatoid arthritis

Approved in Japan as Cellcept for:

• Prevention of acute organ rejection in kidney, liver, and heart transplant patients
• Treatment of autoimmune diseases such as lupus nephritis and rheumatoid arthritis

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Whole-brain radiotherapy (WBRT) combined with temozolomide (TMZ) significantly improves the objective response rate in patients with brain metastases from non-small-cell lung cancer (NSCLC), with a relative risk of 1.43 based on a meta-analysis of 25 clinical trials.

However, this combination treatment also increases the risk of severe hematological (grade III-IV) and gastrointestinal toxicities compared to WBRT alone, indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response and safety of whole-brain radiotherapy plus temozolomide for patients with brain metastases of non-small-cell lung cancer: A meta-analysis. Han, J., Qiu, M., Su, L., et al.[2022]

In a study of 67 patients with newly diagnosed glioblastoma multiforme, the combination of temozolomide, thalidomide, and radiation therapy resulted in a median survival of 73 weeks, indicating a favorable outcome compared to those not receiving adjuvant chemotherapy.

The treatment was generally well tolerated, but the specific benefit of adding thalidomide to temozolomide remains uncertain, as the survival outcomes were similar to those seen with other chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of temozolomide and thalidomide with radiation therapy for newly diagnosed glioblastoma multiforme. Chang, SM., Lamborn, KR., Malec, M., et al.[2018]

In a study of 103 glioblastoma patients treated with standard temozolomide and radiotherapy, the median overall survival was found to be 13.7 months, highlighting the effectiveness of this treatment regimen.

Three key prognostic factors were identified that negatively impacted overall survival: age over 65 years, a Medical Research Council (MRC) scale score of 3-4, and the occurrence of postoperative complications, suggesting that these factors can help predict patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy. Verlut, C., Mouillet, G., Magnin, E., et al.[2020]

In a study of 51 patients with newly diagnosed glioblastoma, concurrent treatment with temozolomide (TMZ) and radiotherapy was found to be the new standard of care.

The occurrence of early necrosis in 14% of patients, without signs of tumor recurrence, suggests that TMZ may enhance the effectiveness of radiotherapy by acting as a radiosensitizer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. Chamberlain, MC., Glantz, MJ., Chalmers, L., et al.[2022]

In a study of 116 patients with glioblastoma multiforme (GBM), treatment with radiotherapy combined with concomitant and adjuvant temozolomide resulted in a median overall survival of 9 months, with 1- and 2-year survival rates of 41.9% and 9.6%, respectively.

Key prognostic factors influencing survival included age, Karnofsky performance scale (KPS) score, presence of seizures, and total radiation doses, all of which were confirmed as significant in both univariate and multivariate analyses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic significance of concomitant radiotherapy in newly diagnosed glioblastoma multiforme: a multivariate analysis of 116 patients. Okumus, NO., Gursel, B., Meydan, D., et al.[2021]

In a study of 79 patients with glioblastoma, the combination of radiotherapy and temozolomide resulted in a median overall survival of 18.3 months and 2-year survival rate of 37.1%, which aligns with previous international studies.

The main side effect observed was hematologic toxicity in 8.8% of patients, indicating that while the treatment is effective, monitoring for blood-related side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome of concomitant chemoradiotherapy followed by adjuvant temozolomide therapy for glioblastaomas: single-center experience. Jeon, HJ., Kong, DS., Park, KB., et al.[2018]

Adding nitrosourea-based chemotherapy to radiotherapy has been shown to increase progression-free survival in patients with grade II and III gliomas, although it does not improve overall survival.

Upcoming phase III trials will investigate whether adding temozolomide to radiotherapy can enhance overall survival in grade II/III gliomas, while also assessing cognitive function and quality of life for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and radiation in low-grade and anaplastic gliomas: temoradiation. Schiff, D.[2018]

Temozolomide, a key chemotherapy drug for glioblastoma, faces significant resistance primarily due to the activation of the O-6-methylguanine-DNA methyltransferase enzyme, which repairs the DNA damage caused by the drug, thus restoring genomic integrity.

Recent research has identified various mechanisms contributing to temozolomide resistance, including indirect DNA repair systems, drug efflux mechanisms, epigenetic changes, and influences from the tumor microenvironment, highlighting the complexity of overcoming this resistance in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide Resistance: A Multifarious Review on Mechanisms Beyond O-6-Methylguanine-DNA Methyltransferase. Rao, V., Kumar, G., Vibhavari, RJA., et al.[2023]

The study determined that the maximum tolerated dose (MTD) of hypofractionated SIB-IMRT combined with temozolomide (TMZ) for treating high-grade gliomas is 3.6 Gy per fraction, with tolerable adverse reactions observed in 16 patients.

Patients treated with this regimen showed promising survival outcomes, with a median overall survival of 19 months and a 1-year overall survival rate of 86.7%, suggesting potential benefits of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of high-grade gliomas using escalating doses of hypofractionated simultaneous integrated boost-intensity-modulated radiation therapy in combination with temozolomide: A modified Phase I clinical trial. Ge, X., Xue, X., Liu, H., et al.[2022]

In a phase II clinical trial involving 21 patients with newly diagnosed glioblastoma multiforme (GBM), the combination of temozolomide (TMZ) with radiotherapy resulted in a one-year survival rate of 58% and a median survival time of 15.7 months, indicating its efficacy in extending survival.

The treatment regimen was well-tolerated, with only mild to moderate non-hematological side effects and minimal severe hematological toxicity, suggesting that TMZ has a favorable safety profile compared to traditional chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. Lanzetta, G., Campanella, C., Rozzi, A., et al.[2018]

In a study of 573 glioblastoma multiforme patients, those treated with temozolomide alongside radiotherapy experienced significantly improved overall survival, with a median survival of 14.6 months compared to 12.1 months for those receiving radiotherapy alone.

The combination treatment was associated with some adverse effects, including thrombocytopenia and nausea, but overall, the benefits in survival rates suggest that temozolomide is an effective option for newly diagnosed glioblastoma multiforme patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food and Drug Administration Drug approval summary: temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme. Cohen, MH., Johnson, JR., Pazdur, R.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11467484/

Recurrence pattern of glioblastoma treated with intensity ... IMRT and 3D-CRT effectively managed glioblastoma with no significant differences in OS and PFS. The survival benefit with GTR underscored the importance of ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425001009

Comparative Outcomes of Standard Radiation Therapy ... In conclusion, our findings suggest that a 5-fraction adaptive stereotactic RT may offer comparable OS, PFS, and local control to 15- and 30-fraction regimens ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10316045/

A Prospective Study of Intensity-modulated Radiation Therapy ... In our prospective trial, 2-year OS rates were 100%, 57%, and 33% in class I/II, IV, and V patients, respectively (p=0.002). Our prospective ...

4. nrgoncology.org nrgoncology.org/Home/News/Post/nrg-oncology-trial-analysis-shows-improvement-in-survival-outcomes-for-glioblastoma-patients-receiving-proton-therapy-trial-moves-to-phase-iii

NRG Oncology Trial Analysis Shows Improvement in ... The recent analysis of the proton cohort revealed improved survival for patients receiving proton therapy at 75 Gy. Because this data met the ...

5. cancerblog.mayoclinic.org cancerblog.mayoclinic.org/2025/01/16/breakthrough-in-treatment-approach-showing-promise-in-the-fight-against-glioblastoma/

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Study Details | NCT05236036 | Mycophenolate Mofetil in ... This phase I/Ib trial tests the safety, side effects, and best dose of mycophenolate mofetil in combination with temozolomide and/or radiation therapy ...

7. cancer.gov cancer.gov/clinicaltrials/NCI-2021-12424

Mycophenolate Mofetil in Combination with Standard of ... This phase I/Ib trial tests the safety, side effects, and best dose of mycophenolate mofetil in combination with temozolomide and/or radiation therapy ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2015

Results from phase 1 study of mycophenolate mofetil with ... Conclusions: MMF can penetrate enhancing and non-enhancing GBM with evidence of successful inhibition of de-novo purine synthesis in humans, and ...

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Mycophenolate Mofetil in Combination With Standard of Care ... This phase I/Ib trial tests the safety, side effects, and best dose of mycophenolate mofetil in combination with temozolomide and/or radiation therapy (standard ...

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Mycophenolate Mofetil in Combination With ... Overview. This phase I/Ib trial tests the safety, side effects, and best dose of mycophenolate mofetil in combination with temozolomide ...