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.
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
| Drug | Synonyms | Arms |
|---|
| Mycophenolate Mofetil | | Phase 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
| Name | Type | Description | Interventions |
|---|
| Phase 0 | Experimental | 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. | |
| Phase 1 | Experimental | 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. | |
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: | Recruiting |
| Lead Sponsor: | University of Michigan Rogel Cancer Center |
Last Updated
November 19, 2020
