Mycophenolate Mofetil + Radiation for Glioblastoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: Bevacizumab, Immunosuppressants

Disqualifiers: HIV, Hepatitis B/C, Organ transplant, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the highest safe dose of Mycophenolate Mofetil (MMF), an immunosuppressant drug, when combined with radiation therapy for treating glioblastoma or gliosarcoma, aggressive brain tumors. The trial includes different groups: one for those with recurrent tumors and another for newly diagnosed patients. Individuals diagnosed with glioblastoma or gliosarcoma who can tolerate standard treatments like surgery or radiation may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to contribute to groundbreaking research.

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 have used bevacizumab within 8 weeks of joining the study. It's best to discuss your current medications with the study team.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot have used bevacizumab within 8 weeks of joining the study, and there are restrictions on certain conditions and treatments. It's best to discuss your specific medications with the trial team.

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

Research shows that Mycophenolate Mofetil (MMF) is under study for safety when combined with radiation therapy and temozolomide, a common cancer drug. Previous studies have tested MMF to determine the best and safest dose with these treatments.

These studies examine patient tolerance and potential side effects. Although still in early stages, MMF has FDA approval for other uses, indicating some known safety. Doctors have experience with it, but its use with radiation and temozolomide for brain cancer remains under exploration.

The studies aim to determine how much MMF can be safely administered with these treatments, ensuring patients can undergo the therapy without serious side effects. Prospective trial participants should know that early studies are still identifying the safest way to use MMF in this new context. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for glioblastoma, which typically involve surgery, radiation, and chemotherapy with drugs like temozolomide, this new approach combines mycophenolate mofetil with radiation therapy. Mycophenolate mofetil is unique because it targets the immune system differently, potentially reducing tumor growth by suppressing immune responses that enable cancer cells to thrive. Researchers are excited because this approach could enhance the effectiveness of radiation therapy and offer a new avenue for treating both recurrent and newly diagnosed glioblastoma. This combination might improve outcomes by attacking the tumor on multiple fronts, offering hope for a condition that has been challenging to treat effectively.

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

Research shows that Mycophenolate Mofetil (MMF) can effectively reach glioblastoma (GBM) tumors and block a process needed for tumor growth. Lab studies have found that MMF enhances the effectiveness of radiation and the chemotherapy drug temozolomide, suggesting it might improve treatment outcomes. In this trial, some participants will receive MMF alone, while others will receive MMF combined with radiation therapy. Additionally, a group of participants will receive a combination of MMF, radiation, and temozolomide. Studies have shown that MMF can lower certain tumor markers, indicating its early effect on glioblastoma. This combination of MMF, radiation, and temozolomide is under study for its potential to help patients with this aggressive brain cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Nathan Clarke, MD

Principal Investigator

University of Michigan Rogel Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with glioblastoma or gliosarcoma, either newly diagnosed or recurrent. They must be candidates for surgery, radiation therapy, and agree to use effective contraception. Excluded are those with serious infections, organ transplants, certain medical conditions like phenylketonuria or hypoxanthine-guanine phosphoribosyl-transferase deficiency, pregnant women, and anyone who can't undergo MRI scans.

Inclusion Criteria

I can care for myself but may need occasional help.

Ability to understand and the willingness to sign a written informed consent.

Patient (men and childbearing age women) agrees to the use of highly effective contraception during study participation and for at least 6 weeks for female patients and 90 days for male patients after final MMF administration.

Exclusion Criteria

My cancer has spread to the lining of my brain and spinal cord.

I have not had chemotherapy or radiation for my newly diagnosed glioblastoma or gliosarcoma.

I have been diagnosed with HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 0

Participants receive Mycophenolate Mofetil (MMF) for one week before undergoing a planned biopsy or re-resection of glioblastoma or gliosarcoma

1 week

1 visit (in-person) for biopsy or re-resection

Phase 1 - Treatment

Participants receive Mycophenolate Mofetil (MMF) combined with radiation therapy, and for newly diagnosed cases, also with temozolomide

Up to 11 weeks

Multiple visits (in-person) for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Mycophenolate Mofetil
• Radiation Therapy

Trial Overview

The study tests the highest dose of Mycophenolate Mofetil (MMF) that patients can tolerate alongside radiation therapy for brain cancer treatment. It's a phase 0/1 trial where doses increase gradually to find the safe limit. Standard treatments like surgery and Temozolomide may also be used.

How Is the Trial Designed?

Group I: Phase 1 - Recurrent GBM / GS Experimental Treatment 2 Interventions

Mycophenolate mofetil; radiation therapy

Group II: Phase 1 - Newly Diagnosed GBM / GS Experimental Treatment 3 Interventions

Mycophenolate mofetil; radiation therapy; temozolomide

Group III: Phase 0 - Recurrent glioblastoma (GBM) / gliosarcoma (GS) Experimental Treatment 2 Interventions

Mycophenolate mofetil

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?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Hypofractionated stereotactic body radiation therapy (SBRT) for early-stage nonsmall cell lung carcinoma was found to be safe and effective, with no significant toxicity reported in a study of nine patients over an 18-month follow-up period.

Using an active breath coordinator (ABC) during treatment resulted in smaller planning target volumes and less lung exposure to radiation compared to free breathing, suggesting that ABC may enhance treatment precision without increasing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for early-stage primary lung cancer, is an active breath coordinator necessary? An audit from a tertiary cancer care center. Madhavan, R., Renilmon, PS., Nair, HM., et al.[2018]

Combining metastasis-directed hypofractionated radiation therapy (RT) with systemic therapies can be effective, but specific timing adjustments are necessary to minimize toxicity; for example, BRAF and MEK inhibitors should be suspended a few days before and after RT due to reported toxicities.

Certain therapies like cetuximab and osimertinib are generally safe with RT, but recommendations include suspending them during radiation treatment to reduce potential side effects, highlighting the need for careful management when integrating these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Metastasis-Directed Radiation Therapy in the Era of Evolving Systemic, Immune, and Targeted Therapies. Guimond, E., Tsai, CJ., Hosni, A., et al.[2022]

Concurrent involved-field radiation therapy (IFRT) and intrathecal chemotherapy (IC) with methotrexate or cytarabine showed a clinical response rate of 34% in 53 patients with leptomeningeal metastasis, indicating its effectiveness as a treatment option.

The treatment had an acceptable safety profile, with 28% of patients experiencing adverse events, and a median overall survival of 6.5 months, suggesting it can be a viable option even for patients who developed leptomeningeal metastasis while on targeted therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of concurrent involved-field radiotherapy and intrathecal chemotherapy for leptomeningeal metastasis from solid tumors. Pan, Z., Chen, K., He, H., et al.[2023]

The combination of anti-GITR monoclonal antibody (mAb) and stereotactic radiosurgery (SRS) significantly improved survival rates in a mouse model of glioblastoma, with a cure rate of 24% compared to 0% for either treatment alone, indicating a strong immune-mediated effect.

The treatment with anti-GITR (1) and SRS led to increased infiltration of CD4+ effector T-cells and enhanced production of immune signaling molecules like IFNγ and IL-2, suggesting that this combination effectively shifts the immune response against the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune-mediated survival advantage in murine intracranial glioma. Patel, MA., Kim, JE., Theodros, D., et al.[2022]

Spirohydantoin mustard (spiromustine) is a promising therapy for glioblastoma multiforme that effectively penetrates the blood-brain barrier and targets brain tumors, potentially improving treatment outcomes.

Intracarotid administration of cisplatin enhances drug delivery directly to the tumor while minimizing systemic exposure, indicating a strategic approach to chemotherapy for better efficacy and safety in treating this aggressive brain cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spiromustine and intracarotid artery cisplatin in the treatment of glioblastoma multiforme. Resio, MJ., DeVroom, HL.[2019]

Radiation oncologists are exploring various innovative approaches, such as interstitial implants and stereotactic radiosurgery, to enhance cure rates for primary brain tumors while aiming to reduce long-term side effects.

These new radiation techniques must be integrated into a comprehensive treatment plan that includes other therapies to effectively manage primary malignant brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving radiotherapy for brain tumors. Woo, SY., Maor, MH.[2005]

Recent advances in radiation therapy for malignant glioma, such as stereotactic radiotherapy and charged particle therapy, aim to improve treatment efficacy while reducing damage to healthy tissues.

Combining these advanced radiation techniques with targeted biochemotherapies may enhance therapeutic outcomes for patients with malignant glioma, which has historically had a poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted radiotherapy for malignant gliomas. Oh, DS., Adamson, DC., Kirkpatrick, JP.[2019]

In a study involving 15 patients with centrally or superiorly located stage I non-small-cell lung cancer (NSCLC), intensity-modulated proton therapy (IMPT) and passive-scattering proton therapy (PSPT) were found to significantly reduce radiation exposure to surrounding healthy tissues compared to conventional photon stereotactic body radiation therapy (SBRT).

IMPT and PSPT plans not only improved tumor coverage but also minimized the maximum tolerated dose to critical structures like the heart and spinal cord, demonstrating their potential for safer treatment options in patients with challenging tumor locations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton stereotactic body radiation therapy for clinically challenging cases of centrally and superiorly located stage I non-small-cell lung cancer. Register, SP., Zhang, X., Mohan, R., et al.[2021]

Combining chemotherapy delivered through intrathecal and intraventricular routes with radiotherapy has led to long-lasting remissions in patients, suggesting the potential for a 'cure' rather than just symptom relief.

A specific treatment protocol that includes radiotherapy followed by intraventricular administration of methotrexate and cytosine arabinoside shows promise in effectively managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of meningeal leukemia. Pochedly, C.[2019]

Intralesional radioimmunotherapy (RAIT) using monoclonal antibodies against tenascin in 24 patients with recurrent malignant gliomas showed promising results, with a median survival time of 16 months and several patients achieving tumor stabilization or remission.

The treatment demonstrated a favorable safety profile, with no systemic or brain toxicities reported, and only a few cases of human anti-mouse antibody production, indicating that RAIT could be a viable option for managing these aggressive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intralesional radioimmunotherapy of malignant gliomas. An effective treatment in recurrent tumors. Riva, P., Arista, A., Tison, V., et al.[2019]

In a study of 68 patients with advanced solid tumors, the combination of stereotactic body radiotherapy (SBRT) followed by pembrolizumab showed a high one-year treated metastasis control rate of 89.5%, indicating effective tumor response regardless of whether the tumors received complete or partial radiation coverage.

The study found that treated metastasis control (TMC) was significantly associated with improved overall survival, and SBRT altered tumor gene expression by increasing immune-related genes while decreasing those related to cell cycle and DNA repair, suggesting a mechanism for enhanced immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. Luke, JJ., Onderdonk, BE., Bhave, SR., et al.[2021]

Radiation therapy is crucial for treating adult brain tumors, but its application is changing based on tumor type, with ongoing trials exploring how to enhance its effectiveness and minimize side effects.

For low-grade gliomas, researchers are focusing on identifying patients who can safely delay radiation until necessary, while in cases like meningioma, advanced techniques like radiosurgery are improving outcomes for patients with a good prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation oncology in brain tumors: current approaches and clinical trials in progress. Chan, MD., Tatter, SB., Lesser, G., et al.[2022]

A 68-year-old man with metastatic lung cancer developed myelitis after receiving radiotherapy and immunotherapy, but he fully recovered after stopping pembrolizumab and receiving steroid treatment, indicating that while both treatments can have serious side effects, recovery is possible with appropriate management.

This case suggests a potential interaction between radiotherapy and immunotherapy that may lead to delayed radiation myelopathy, but it also highlights that rechallenging with immunotherapy can be safe, as the patient remained in response without relapse of myelitis after resuming treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation myelitis after pembrolizumab administration, with favorable clinical evolution and safe rechallenge: a case report and review of the literature. Carausu, M., Beddok, A., Langer, A., et al.[2020]

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