A Phase 1 interventional study of Mycophenolate Mofetil and Quality-of-Life Assessment in Astrocytoma, Glioblastoma and Glioblastoma, IDH-Wildtype, sponsored by Northwestern University. Active, not recruiting at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-26.
Sponsored by Northwestern University · Phase 1, Interventional, and Treatment
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.
PRIMARY OBJECTIVE:
I. To evaluate the recommended phase 2 dose (RP2D) for mycophenolate mofetil (MMF) in combination with radiation therapy as well as in combination with temozolomide (TMZ).
II. Phase 1b (Groups 3 and R): To estimate median and corresponding 95% CI for progression-free survival (PFS) and overall survival (OS).
III. Phase 0 (Group S; Sub-Group S1 and Sub-Group S2): To evaluate drug uptake and target effect in the brain.
SECONDARY OBJECTIVES:
I. To evaluate the safety profile of mycophenolate mofetil (MMF) in combination with temozolomide (TMZ).
II. To estimate progression free survival (PFS) per Response Assessment in Neuro-Oncology Criteria (RANO).
III. To estimate overall survival (OS). IV. To estimate the overall response rate (ORR) per RANO criteria. V. To evaluate quality of life per Functional Assessment of Cancer Therapy Scale-Brain (FACT-Br) for patients treated with mycophenolate mofetil and/or temozolomide.
EXPLORATORY OBJECTIVES:
I. To investigate the relationship between the molecular signature of individual glioblastoma multiforme (GBM) with clinical outcome, by measuring levels of serum mycophenolic acid in patient's plasma post MMF administration.
Ia. Perform molecular characterization of all GBM tissues by ribonucleic acid sequencing (RNAseq) analysis.
Ib. Perform bulk metabolomics for GBM tissue. Ic. Measure plasma and serum concentration of mycophenolic acid, the MMF's primary active metabolite, during and after combination therapy.
Id. Measure IMPDH activity assay in patients' peripheral blood mononuclear cells (PBMCs) as well as in GBM tissue.
Ie. Analyze relevant gene mutations from standard of care next generation sequencing (NGS) tumor gene mutation data, if available. II. Group R only: To assess early efficacy of mycophenolate mofetil (MMF) in combination with temozolomide (TMZ) in recurrent GBM.
OUTLINE: This is a dose-escalation study of MMF (Part 1), followed by a dose-expansion study (Part 2).
PART 1: Patients are assigned to 1 of 3 groups.
GROUP 1: Patients who have already undergone surgery or biopsy followed by chemoradiation receive TMZ orally (PO) once daily (QD) on days 1-5 of each cycle and MMF PO twice daily (BID). Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
GROUP 2: 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 S: 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.
PART 2: Patients are assigned to Group 3 or enrolled to Group R.
GROUP 3: 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.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 18 months.
Group R (Recurrent): MMF + TMZ at MTD. Enrollment to begin concurrently with Group 3.Group R will be given the MTD for temozolomide + MMF via the same schedule and dosing as the adjuvant group (Group 1) and will open once the RP2D from Group 1 has been determined. Patients 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.
420 studies on the registry are indexed under Astrocytoma; 76 are open to participants now.
This study's enrollment of 86 is above the median of 30 across 346 interventional studies indexed under Astrocytoma.
Browse Astrocytoma studies →Northwestern University is the lead sponsor of 1,396 studies on the registry; 199 are open to participants now.
Of its 102 completed or terminated interventional studies of FDA-regulated products, 73 (72%) have results posted.
Counted across the registry records on this site, refreshed daily.
GROUPS 1-3: Newly diagnosed glioblastoma and:
Stable or decreasing dose of corticosteroids equivalent to =\< 8 mg dexamethasone daily, for >= 7 days prior to registration.
Females of child-bearing potential (FOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of informed consent, for the duration of study participation, and for 3 months following completion of therapy. Should a female patient become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception from time of informed consent, for the duration of study participation, and 4 months after completion of administration.
NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
Patient or their legally authorized representative must provide written, signed, and dated informed consent prior to study registration. Patient or their legally authorized representative (LAR) must have the ability to understand and the willingness to sign a written informed consent document. The patient or their LAR must be willing and able to comply with the protocol for the duration of the study.
Exclusion Criteria:
Patients who are receiving any other investigational agents.
Patient who have a prior or concurrent malignancy that may interfere with study treatment or safety.
Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
Patients with a known history of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV).
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
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
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
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
Group R (Recurrent): MMF + TMZ at MTD. Patients 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
Given PO
Also known as: CellCept, MMF
Ancillary studies
Also known as: Quality of Life Assessment
Receive radiation therapy
Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
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
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.
Time frame: 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.
Time frame: Up to 6 weeks + 7 days
Frequency of adverse events
The occurrence of toxicity (including \[AEs\] and serious adverse events \[SAEs\]), and the number of patients who discontinue treatment due to toxicity, as assessed by CTCAE v. 5.0. This endpoint will collect and report the frequency of adverse events by type, severity (grade), timing, and attribution to MMF, according the National Cancer Institute (NCI)-CTCAE v. 5.0.
Time frame: Up to 30 days after completion of study treatment
Progression Free Survival (PFS)
Progression will be determined by clinical progression or by radiographic imaging as assessed by Response Assessment in Neuro-Oncology Criteria (RANO). If disease progression or death from any cause is not observed prior to initiating subsequent anti-cancer therapy or completing study participation, the PFS will be censored as the last available disease assessment. Kaplan-Meier curves will be plot. Log-rank test will be used to compare it with historical standard care control in literature.
Time frame: 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)
If death from any cause is not observed prior to initiating subsequent anti-cancer therapy or completing study participation, the OS will be censored as the last available follow-up. will be described by Kaplan-Meier curve. The median and corresponding 95% confidence interval will also be estimated.
Time frame: 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)
Overall response rate will be assessed by RANO criteria. To determine the ORR, this endpoint will calculate the proportion of treated patients who experience an overall response (complete response \[CR\] or partial response \[PR\] per RANO criteria). The date of first response for either CR or PR will be used for the calculation of ORR. Will be estimated using the expansion cohort, along with its 95% confidence interval.
Time frame: 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)
The quality of life indicated by FACT-Br will be evaluated by estimating its mean, standard deviation and 95% confidence interval using the expansion cohort. Patients who received at least 1 dose of temozolomide (TMZ) and/or MMF, and completed at least baseline and cycle 2 day 1 (C2D1) FACT-Br QOL (for Groups 1-3) will be evaluable for this secondary endpoint.
Time frame: Up to 6 cycles (1 cycle = 28 days)
Mycophenolic acid levels
Will measure in patients' plasma by using the Food and Drug Administration (FDA)-approved protocol Analytical Chemistry Division at the Illinois Institute of Technology Research Institute.
Time frame: Days 1, 3 and 7 post-MMF administration for cycles 1 and 2
XMP concentration
Will utilize an established clinical protocol and a highly sensitive liquid chromatography-mass spectrometry method in peripheral blood mononuclear cells (PBMCs) isolated from glioblastoma patients receiving MMF in combination with TMZ in order to determine IMPDH activity. This is a clinically validated protocol in which the analytical methods yielded acceptable within samples and within individual variability. Peripheral blood samples taken at baseline and day 1 of each adjuvant TMZ+MMF cycle will be used to test this.
Time frame: Up to 6 cycles (1 cycle = 28 days)
This study is active, not recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Northwestern University