Mycophenolate Mofetil in Combination With Standard of Care for the Treatment of Glioblastoma

NCT05236036 | Active Not Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: NU 21C01NCI-2021-12424STU00215766P30CA060553
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

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 of care) in treating patients with glioblastoma. Mycophenolate mofetil is an immunosuppressant drug that is typically used to prevent organ rejection in transplant recipients. However, mycophenolate mofetil may also help chemotherapy with temozolomide work better by making tumor cells more sensitive to the drug. The purpose of this trial is to determine if mycophenolate mofetil combined with temozolomide can stop glioblastoma.

Conditions

Astrocytoma; Glioblastoma; Glioblastoma, IDH-Wildtype; MGMT-Unmethylated Glioblastoma; Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) for mycophenolate mofetil (MMF) (Group 1)

  Will be based on treatment-emergent and drug related toxicity of grade \>= 3 during the first cycle of treatment. MTD indicates maximum tolerated dose for dose limiting toxicity (DLT). DLT is defined as side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. Recommended phase 2 dose (RP2D) is the highest dose of a drug or treatment that does not cause unacceptable side effects. For the purposes of this study, RP2D is interchangeable with MTD. DLTs and Adverse Events (AEs) will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v). 5.0.

  Up to completion of first cycle of treatment + 7 days (1 cycle = 28 days)

• MTD/RP2D for MMF (Group 2)

  Will be based on treatment-emergent and drug related toxicity of grade \>= 3 during focal radiation treatment. MTD indicates maximum tolerated dose for DLT. DLT is defined as side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. RP2D is the highest dose of a drug or treatment that does not cause unacceptable side effects. For the purposes of this study, RP2D is interchangeable with MTD. DLTs and AEs will be assessed by CTCAE v.5.0.

  Up to 6 weeks + 7 days

Secondary Outcomes (5)

• Frequency of adverse events

  Up to 30 days after completion of study treatment

• Progression Free Survival (PFS)

  From baseline until the patient experiences disease progression, initiates subsequent anti-cancer therapy, completes study participation, or experiences death from any cause (whichever is sooner), assessed up to 18 months

• Overall survival (OS)

  From time of diagnosis until the patient initiates subsequent anti-cancer therapy, completes study participation, or experiences death from any cause (whichever is sooner), assessed up to 18 months

• Overall response rate (ORR)

  From baseline, the patient experiences disease progression, the patient initiates subsequent anti-cancer therapy, or the patient completes study participation (whichever occurs first), assessed up to 18 months

• Quality of life (QOL)

  Up to 6 cycles (1 cycle = 28 days)

Other Outcomes (2)

• Mycophenolic acid levels

  Days 1, 3 and 7 post-MMF administration for cycles 1 and 2

• XMP concentration

  Up to 6 cycles (1 cycle = 28 days)

Study Arms (4)

Group 1 (TMZ, MMF)

EXPERIMENTAL

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.

Drug: Mycophenolate Mofetil; Other: Quality-of-Life Assessment; Drug: Temozolomide

Group 2 (TMZ, MMF, radiation therapy)

EXPERIMENTAL

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.

Drug: Mycophenolate Mofetil; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy; Drug: Temozolomide

Group 3 (TMZ, MMF, radiation therapy)

EXPERIMENTAL

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.

Drug: Mycophenolate Mofetil; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy; Drug: Temozolomide

Group S (pre-surgical MMF, TMZ)

EXPERIMENTAL

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.

Drug: Mycophenolate Mofetil; Other: Quality-of-Life Assessment; Drug: Temozolomide

Interventions

Mycophenolate Mofetil DRUG

Given PO

Also known as: CellCept, MMF

Group 1 (TMZ, MMF); Group 2 (TMZ, MMF, radiation therapy); Group 3 (TMZ, MMF, radiation therapy); Group S (pre-surgical MMF, TMZ)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Group 1 (TMZ, MMF); Group 2 (TMZ, MMF, radiation therapy); Group 3 (TMZ, MMF, radiation therapy); Group S (pre-surgical MMF, TMZ)

Radiation Therapy RADIATION

Receive radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Group 2 (TMZ, MMF, radiation therapy); Group 3 (TMZ, MMF, radiation therapy)

Temozolomide DRUG

Given Orally (PO)

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ

Group 1 (TMZ, MMF); Group 2 (TMZ, MMF, radiation therapy); Group 3 (TMZ, MMF, radiation therapy); Group S (pre-surgical MMF, TMZ)

Eligibility Criteria

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

You may qualify if:

• GROUPS 1-3: Histologically confirmed glioblastoma (GBM), IDH wild-type (by immunohistochemistry \[IHC\] R132H negative \[neg\] or sequencing). Astrocytoma with molecular features of GBM are eligible.
• GROUPS 1-3: Newly diagnosed glioblastoma and:
• Group 1: Received surgical resection or biopsy followed by chemoradiation;
• Group 2: Received surgical resection or biopsy only and have documented unmethylated glioblastoma (may have been done at an outside facility);
• Group 3: Received surgical resection or biopsy only
• GROUP S: Newly suspected glioblastoma or recurrent glioblastoma, and scheduled to undergo a standard of care surgical resection or biopsy.
• Stable or decreasing dose of corticosteroids equivalent to =\< 8 mg dexamethasone daily, for \>= 7 days prior to registration.
• Note: There are no restrictions on steroid use on study
• Patients must be age \>= 18 years.
• Patients must exhibit a Karnofsky performance status \>= 70.
• Leukocytes (white blood cells \[WBC\]) \>= 3,000/mcL (within 14 days prior to study registration)
• Absolute neutrophil count (ANC) \>= 1,500/mcL (within 14 days prior to study registration)
• Hemoglobin (Hgb) \>= 8 g/dL (within 14 days prior to study registration) (transfusion may be used for eligibility if \>= 7 days)
• Platelets (PLT) \>= 100,000/mcL (within 14 days prior to study registration) (transfusion or growth factor may be used for eligibility if \>= 7 days).
• Total bilirubin =\< 2x institutional upper limit of normal (ULN) (within 14 days prior to study registration)

You may not qualify if:

• Patients who are receiving any other investigational agents.
• Exception: COVID-19 vaccine and treatment is allowed
• Patient who have a prior or concurrent malignancy that may interfere with study treatment or safety.
• NOTE: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible. Per principal investigator (PI) discretion
• Patients who have a history of allergic reactions attributed to compounds of similar chemical composition to temozolomide or mycophenolate mofetil.
• Patients with spinal cord and diffuse leptomeningeal disease GBM
• Patients requiring live vaccinations within 2 weeks of initiation of MMF and/or TMZ therapy. Consider completion of vaccination with live vaccines prior to starting immunosuppressive therapy, as indicated.
• Patients on viral-vector based therapy due to increased risk for disseminated herpetic infection.
• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
• Have uncontrolled epilepsy
• Have an uncontrolled intercurrent illness
• Concurrent malignancy (outside of glioblastoma) that requires tumor directed treatment
• Known deficiency of hypoxanthine-guanin-phosphoribosyltransferase (HGPRT) deficiency, e.g. Lesch-Nyhan- oder Kelley-Seegmiller-Syndrome.
• Known concurrent shingles, herpes, CMV (cytomegalovirus) infection
• Known concurrent opportunistic fungal infection

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Northwestern Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

Northwestern Medicine Warrenville

Warrenville, Illinois, 60555, United States

Location

MeSH Terms

Conditions

Astrocytoma; Glioblastoma

Interventions

Mycophenolic Acid; Radiotherapy; Radiation; Temozolomide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Therapeutics; Physical Phenomena; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Priya U Kumthekar, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2022
• First Posted: February 11, 2022
• Study Start: August 8, 2022
• Primary Completion: January 12, 2026
• Study Completion (Estimated): January 3, 2029
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

US (3)