Mycophenolate Mofetil Combined With Radiation Therapy in Glioblastoma

NCT04477200 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: UMCC 2019.192HUM00175785R37CA258346
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 0/1 dose-escalation trial to determine the maximum tolerated dose of Mycophenolate Mofetil (MMF) when administered with radiation, in patients with glioblastoma or gliosarcoma.

Conditions

Recurrent Glioblastoma; Recurrent Gliosarcoma; Recurrent Astrocytoma, Grade IV; Newly Diagnosed Glioblastoma; Newly Diagnosed Gliosarcoma; Newly Diagnosed Astrocytoma, Grade IV

Keywords

recurrent Glioblastoma; recurrent Gliosarcoma; newly diagnosed Glioblastoma; newly diagnosed Gliosarcooma; Recurrent Astrocytoma, Grade IV; Newly Diagnosed Astrocytoma, Grade IV

Outcome Measures

Primary Outcomes (4)

• Concentration of mycophenolic acid (MPA) in tumor tissue in Phase 0 participants

  The concentration of MPA (the active metabolite of mycophenolate mofetil \[MMF\]) in tumor tissue, measured by mass spectrometry on a continuous scale after one week of MMF administration. This measure includes all phase 0 participants.

  At 1 week

• Number of recurrent phase 1 participants who experience dose-limiting toxicities (DLTs) at each dose level

  DLT will be defined based on the rate of drug related grade 3-5 adverse events experienced from the start of treatment with MMF and for up to 4 weeks after completion of MMF + radiation therapy (RT). Assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. This measure includes only phase 1 participants with recurrent GBM/GS.

  Up to 28 days following completion of MMF + RT (up to ~9 weeks)

• Number of newly diagnosed phase 1 participants who experience dose-limiting toxicities (DLTs) at each dose level -- DLT1 period

  DLT will be defined based on the rate of drug related grade 3-5 adverse events experienced from the start of treatment with MMF and for up to 4 weeks after completion of MMF + RT + TMZ. Assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. This measure includes only newly diagnosed phase 1 participants.

  Up to 28 days following completion of MMF + RT + TMZ (up to ~11 weeks)

• Number of newly diagnosed phase 1 participants who experience dose-limiting toxicities (DLTs) at each dose level -- DLT2 period

  DLT will be defined based on the rate of drug related grade 3-5 adverse events experienced during the first 2 cycles (8 weeks) of MMF with adjuvant TMZ. (The first cycle of MMF with adjuvant TMZ begins 28 days post-RT.) These will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. This measure includes only newly diagnosed phase 1 participants.

  During the first 2 cycles (8 weeks) of MMF with adjuvant TMZ (up to ~19 weeks)

Secondary Outcomes (7)

• Concentrations of guanosine triphosphate (GTP) in tumor tissue in Phase 0 participants

  After one week of MMF administration

• Adverse events associated with treatment in all Phase 1 Participants

  Up to 28 days following completion of MMF + RT (up to ~9 weeks)

• Adverse events associated with treatment in newly diagnosed phase 1 participants

  Up to 28 days following completion of MMF with adjuvant temozolomide (up to ~15 months)

• Overall Response Rate in phase 1 participants with recurrent GBM/GS

  Until study stops or death; up to approximately 3 years.

• Median Progression Free Survival (PFS) in phase 1 participants with recurrent GBM/GS

  Until study stops or death; up to approximately 3 years.

Study Arms (3)

Phase 0 - Recurrent glioblastoma (GBM) / gliosarcoma (GS)

EXPERIMENTAL

Mycophenolate mofetil

Drug: Mycophenolate Mofetil; Procedure: Re-resection (as part of standard of care)

Phase 1 - Recurrent GBM / GS

EXPERIMENTAL

Mycophenolate mofetil; radiation therapy

Radiation: Radiation Therapy; Drug: Mycophenolate Mofetil

Phase 1 - Newly Diagnosed GBM / GS

EXPERIMENTAL

Mycophenolate mofetil; radiation therapy; temozolomide

Drug: Temozolomide; Drug: Mycophenolate Mofetil; Radiation: Radiation Therapy

Interventions

Mycophenolate Mofetil DRUG

500-2000mg orally twice daily, one week prior to re-resection (2 participants at each of 4 dose levels: 500mg, 1000mg, 1500mg and 2000mg)

Also known as: MMF

Phase 0 - Recurrent glioblastoma (GBM) / gliosarcoma (GS)

Radiation Therapy RADIATION

40.5 Gy in 15 fractions

Also known as: RT

Phase 1 - Recurrent GBM / GS

Re-resection (as part of standard of care) PROCEDURE

Re-resection or biopsy of tumor as part of standard of care

Phase 0 - Recurrent glioblastoma (GBM) / gliosarcoma (GS)

Temozolomide DRUG

Temozolomide capsules are an approved oral chemotherapeutic drug for the treatment of adult patients with newly diagnosed GBM/GS concomitantly with radiotherapy and then as adjuvant treatment. The dosing and timing of temozolomide therapy will be determined as per standard-of-care for the individual patient by the treating oncologist.

Also known as: TMZ

Phase 1 - Newly Diagnosed GBM / GS

Eligibility Criteria

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

You may qualify if:

• Glioblastoma or gliosarcoma (recurrent or newly diagnosed).
• Karnofsky Performance Status 60 or greater.
• Phase 0: Candidate for clinically indicated re-resection or biopsy of glioblastoma or gliosarcoma per treating physician(s).
• Phase 1, Recurrent: Candidate for clinically indicated re-irradiation of glioblastoma or gliosarcoma per treating physician(s) (No more than one prior course of radiation for GBM).
• Phase 1, Newly Diagnosed: Candidate for upfront standard of care chemoradiation for glioblastoma or gliosarcoma per treating physician(s), to start no earlier than 14 days post- operatively from last definitive surgery for glioblastoma or gliosarcoma (if more than one surgery done. Ex. biopsy prior to resection).
• ANC \>=1,500 cells/mm\^3 within 14 days prior to enrollment.
• 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.
• Ability to understand and the willingness to sign a written informed consent.

You may not qualify if:

• Lack of histopathological diagnosis of the tumor.
• Gliomatosis cerebri pattern (tumor involving 3 or more lobes) of disease.
• Leptomeningeal disease.
• Use of bevacizumab within 8 weeks of study enrollment.
• Known history of HIV.
• Active hepatitis B or C infection.
• Active systemic or central nervous system (CNS) infection.
• Grade 4 lymphopenia (if ALC \<0.5, patient must be on Pneumocystis jirovecii prophylaxis).
• Estimated CrCl \< 25 ml/min.
• History of organ transplantation.
• Patients with known hypoxanthine-guanine phosphoribosyl-transferase deficiency.
• Serious intercurrent disease.
• History of allergic reaction or hypersensitivity to mycophenolate mofetil or mycophenolic acid or any component of the drug product; or medical contraindication for MMF per treating physician(s).
• Known immunosuppressive condition from autoimmune disease, immune deficiency syndrome, or chronic immunosuppressive therapy.
• Inability to undergo MRI brain with and without contrast.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Zhao G, Newbury P, Ishi Y, Chekalin E, Zeng B, Glicksberg BS, Wen A, Paithankar S, Sasaki T, Suri A, Nazarian J, Pacold ME, Brat DJ, Nicolaides T, Chen B, Hashizume R. Reversal of cancer gene expression identifies repurposed drugs for diffuse intrinsic pontine glioma. Acta Neuropathol Commun. 2022 Oct 23;10(1):150. doi: 10.1186/s40478-022-01463-z.

  PMID: 36274161 DERIVED

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

Mycophenolic Acid; Radiotherapy; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; 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; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nathan Clarke, MD

  University of Michigan Rogel Cancer Center

  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

Model Details: Phase 0 will include 8 participants; eligible participants from phase 0 may continue on to phase 1.

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: July 20, 2020
• Study Start: August 5, 2020
• Primary Completion: January 6, 2025
• Study Completion (Estimated): November 5, 2027
• Last Updated: June 29, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)