Clinical Trials /

Mycophenolate Mofetil Combined With Radiation Therapy in Recurrent Glioblastoma

NCT04477200

Description:

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.

Related Conditions:
  • Glioblastoma
  • Gliosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Mycophenolate Mofetil Combined With Radiation Therapy in Recurrent Glioblastoma
  • Official Title: Phase 0/I Dose Escalation Study of Mycophenolate Mofetil Combined With Radiation Therapy in Recurrent Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2019.192
  • SECONDARY ID: HUM00175785
  • NCT ID: NCT04477200

Conditions

  • Recurrent Glioblastoma
  • Recurrent Gliosarcoma

Interventions

DrugSynonymsArms
Mycophenolate MofetilPhase 0

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 0ExperimentalMycophenolate 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.
  • Mycophenolate Mofetil
Phase 1ExperimentalMycophenolate 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.
  • Mycophenolate Mofetil

Eligibility 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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:Phase 0: Concentrations of guanosine triphosphate (GTP) in tumor tissue
Time Frame:After one week of MMF administration
Safety Issue:
Description:The concentrations of GTP in tumor tissue, measured by mass spectrometry on a continuous scale.
Measure:Phase 0: Concentrations of guanosine triphosphate (GTP) in plasma
Time Frame:After one week of MMF administration
Safety Issue:
Description:The concentrations of GTP in plasma, measured by mass spectrometry on a continuous scale.
Measure:Phase 1: Adverse events associated with MMF + re-irradiation
Time Frame:Up to 28 days following completion of radiation and MMF
Safety Issue:
Description:Toxicities at each dose level will be tabulated, categorized by grade and attribution.
Measure:Phase 1: Overall Response Rate
Time Frame:Until study stops or death; up to approximately 3 years.
Safety Issue:
Description: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.
Measure:Phase 1: Median Progression Free Survival (PFS)
Time Frame:Until study stops or death; up to approximately 3 years.
Safety Issue:
Description: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
Measure:Phase 1: Median Freedom from Local Progression (FFLP)
Time Frame:Until study stops or death; up to approximately 3 years.
Safety Issue:
Description:FFLP defined as time from date of registration to the date of documented local progressive disease. Determined by standard RANO criteria
Measure:Phase 1: Median Overall Survival (OS)
Time Frame:Until study stops or death; up to approximately 3 years.
Safety Issue:
Description:OS defined as time from date of registration to date of death or last follow up.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

Last Updated

July 20, 2020