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Mycophenolate Mofetil Combined With Radiation Therapy in Recurrent Glioblastoma

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ClinicalTrials.gov Identifier: NCT04477200
Recruitment Status : Not yet recruiting
First Posted : July 20, 2020
Last Update Posted : July 21, 2020
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

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 recurrent glioblastoma or recurrent gliosarcoma.

Condition or disease Intervention/treatment Phase
Recurrent Glioblastoma Recurrent Gliosarcoma Drug: Mycophenolate Mofetil Radiation: Radiation Therapy Procedure: Re-resection (as part of standard of care) Phase 1

Detailed Description:
The goal of the Phase 0 component is to determine if MMF achieves active concentrations in brain tumors. Eight participants in Phase 0 will receive MMF for one week before undergoing an already planned biopsy or re-resection (surgical removal) of glioblastoma (GBM). A small portion of the tumor, removed as part of clinical care, will be used for testing in this study. Thirty additional participants will be enrolled in the Phase 1 component of the trial. The goal of the Phase 1 component is to find the dose of MMF that works best without causing severe side effects (the maximum tolerated dose) when combined with radiation. Participants in Phase 0 who meet the eligibility criteria for the Phase 1 component may participate in both phases.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 0/I Dose Escalation Study of Mycophenolate Mofetil Combined With Radiation Therapy in Recurrent Glioblastoma
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : November 2024
Estimated Study Completion Date : November 2027


Arm Intervention/treatment
Experimental: Phase 0
Mycophenolate mofetil, administered at 4 dose levels (2 participants will be assigned to each dose level): 500mg, 1000mg, 1500mg and 2000mg, orally, twice daily for one week prior to re-resection or biopsy. The re-resection or biopsy of tumor is part of standard of care.
Drug: Mycophenolate Mofetil
Given PO

Procedure: Re-resection (as part of standard of care)
Re-resection or biopsy of tumor as part of standard of care

Experimental: Phase 1
Mycophenolate mofetil, 250-2000mg orally twice daily, for one week prior to and concurrent with re-irradiation. Radiation therapy of 40.5 Gy in 15 fractions.
Drug: Mycophenolate Mofetil
Given PO

Radiation: Radiation Therapy
40.5 Gy in 15 fractions




Primary Outcome Measures :
  1. Phase 0: Concentration of mycophenolic acid (MPA) in tumor tissue [ Time Frame: After one week of MMF administration ]
    The concentration of MPA (the active metabolite of mycophenolate mofetil [MMF]) in tumor tissue, measured by mass spectrometry on a continuous scale.

  2. Phase 1: Number of participants who experience dose-limiting toxicities (DLTs) at each dose level [ Time Frame: Up to 28 days following completion of radiation and MMF ]
    DLT defined per protocol and assessed per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0


Secondary Outcome Measures :
  1. Phase 0: Concentrations of guanosine triphosphate (GTP) in tumor tissue [ Time Frame: After one week of MMF administration ]
    The concentrations of GTP in tumor tissue, measured by mass spectrometry on a continuous scale.

  2. Phase 0: Concentrations of guanosine triphosphate (GTP) in plasma [ Time Frame: After one week of MMF administration ]
    The concentrations of GTP in plasma, measured by mass spectrometry on a continuous scale.

  3. Phase 1: Adverse events associated with MMF + re-irradiation [ Time Frame: Up to 28 days following completion of radiation and MMF ]
    Toxicities at each dose level will be tabulated, categorized by grade and attribution.

  4. Phase 1: Overall Response Rate [ Time Frame: Until study stops or death; up to approximately 3 years. ]
    Determined by standard Response Assessment for Neuro-Oncology (RANO) criteria. The number and proportion of patients wtih progressive disease, stable disease, partial and complete response will be calculated for each dose level and overall.

  5. Phase 1: Median Progression Free Survival (PFS) [ Time Frame: Until study stops or death; up to approximately 3 years. ]
    PFS defined as time from date of registration to the date of documented progressive disease, other disease related therapy or death. Determined by standard RANO criteria

  6. Phase 1: Median Freedom from Local Progression (FFLP) [ Time Frame: Until study stops or death; up to approximately 3 years. ]
    FFLP defined as time from date of registration to the date of documented local progressive disease. Determined by standard RANO criteria

  7. Phase 1: Median Overall Survival (OS) [ Time Frame: Until study stops or death; up to approximately 3 years. ]
    OS defined as time from date of registration to date of death or last follow up.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recurrent GBM or recurrent gliosarcoma
  • Karnofsky Performance Status 60 or greater
  • Candidate for clinically indicated re-resection or biopsy of glioblastoma or gliosarcoma per treating physician(s) (Phase 0)
  • Candidate for clinically indicated re-irradiation of glioblastoma or gliosarcoma per treating physician(s) (Phase 1)

Exclusion Criteria:

  • Gliomatosis cerebri pattern (involving 3 or more different lobes) of disease
  • Leptomeningeal disease
  • Not willing to adhere to contraception (men and childbearing age women)
  • Known history of HIV
  • Active hepatitis B or C infection
  • Active systemic of central nervous system (CNS) infection
  • Serious intercurrent disease
  • Increase in steroid requirement within 7 days of study enrollment (stable or decreasing dose allowed)
  • Use of bevacizumab within 8 weeks of study enrollment
  • Radiation within 6 months prior to study enrollment (phase I)
  • Surgery within 4 weeks of re-irradiation (phase I)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04477200


Locations
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United States, Michigan
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, United States, 48109
Principal Investigator: Yoshie Umemura, M.D.         
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Investigators
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Principal Investigator: Yoshie Umemura, MD University of Michigan Rogel Cancer Center
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Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT04477200    
Other Study ID Numbers: UMCC 2019.192
HUM00175785 ( Other Identifier: University of Michigan )
First Posted: July 20, 2020    Key Record Dates
Last Update Posted: July 21, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Mycophenolic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action