Mycophenolate Mofetil Combined With Radiation Therapy in... | NCT04477200

ID	Type	Description	Link
HUM00175785	Other Identifier	University of Michigan
R37CA258346	U.S. NIH Grant/Contract		View source

Name	Class
National Cancer Institute (NCI)	NIH

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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)	Phase 0 - Recurrent glioblastoma (GBM) / gliosarcoma (GS)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.

Secondary Outcomes

Measure	Description	Time Frame
Concentrations of Guanosine Triphosphate (GTP) in Tumor Tissue in Phase 0 Participants	The concentrations of GTP in tumor tissue, measured by mass spectrometry on a continuous scale. This measure includes all phase 0 participants.	After one week of MMF administration
Adverse Events Associated With Treatment in All Phase 1 Participants

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.
Pregnant or lactating women.
Patients with known phenylketonuria.
Phase 0: Patients undergoing biopsy who are deemed unlikely to have sufficient tissue to spare for research purposes (e.g., those whose tumors are in an eloquent brain location where all tissue taken must be used for diagnostic purposes).
Phase I: Increase in steroid requirement within 7 days of study enrollment (stable or decreasing dose allowed).
Phase I, Recurrent: Radiation within 6 months prior to study enrollment.
Phase I, Recurrent: Surgery within 4 weeks of re-irradiation.
Phase I, Newly Diagnosed: History of hypersensitivity reactions to temozolomide or any other ingredients in temozolomide and dacarbazine.
Phase I, Newly Diagnosed: Prior chemotherapy or radiation therapy for glioblastoma or gliosarcoma.

Name	Affiliation	Role
Nathan Clarke, MD	University of Michigan Rogel Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Michigan Rogel Cancer Center		Ann Arbor	Michigan	48109	United States

PubMed Identifier	Type	Citation	Retractions
36274161	Derived	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.

ID	Title	Description
FG000	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 2	Mycophenolate mofetil Mycophenolate Mofetil: 500mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
FG001	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 3

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 22, 2023

Arm/Group Information

ID	Title	Description
BG000	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 2	Mycophenolate mofetil Mycophenolate Mofetil: 500mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
BG001	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 3	Mycophenolate mofetil Mycophenolate Mofetil: 1000mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
BG002	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 4	Mycophenolate mofetil Mycophenolate Mofetil: 1500mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
BG003	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 5	Mycophenolate mofetil Mycophenolate Mofetil: 2000mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
BG004	Phase 1 - Recurrent GBM / GS - Level 3	Mycophenolate mofetil; radiation therapy Radiation Therapy: 40.5 Gy in 15 fractions Mycophenolate Mofetil: 1000mg orally twice daily, one week prior to and concurrent with RT.
BG005	Phase 1 - Recurrent GBM / GS - Level 4	Mycophenolate mofetil; radiation therapy Radiation Therapy: 40.5 Gy in 15 fractions Mycophenolate Mofetil: 1500mg orally twice daily, one week prior to and concurrent with RT.
BG006	Phase 1 - Recurrent GBM / GS - Level 5	Mycophenolate mofetil; radiation therapy Radiation Therapy: 40.5 Gy in 15 fractions Mycophenolate Mofetil: 2000mg orally twice daily, one week prior to and concurrent with RT.
BG007	Phase 1 - Newly Diagnosed GBM / GS - Level 3	Mycophenolate mofetil; radiation therapy; temozolomide Temozolomide: 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. Mycophenolate Mofetil: 1000mg orally twice daily, one week prior to and concurrent with RT and cyclic chemotherapy with temozolomide. Radiation Therapy: 60 Gy in 30 fractions
BG008	Phase 1 - Newly Diagnosed GBM / GS- Level 4	Mycophenolate mofetil; radiation therapy; temozolomide Temozolomide: 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. Mycophenolate Mofetil: 1500mg orally twice daily, one week prior to and concurrent with RT and cyclic chemotherapy with temozolomide. Radiation Therapy: 60 Gy in 30 fractions
BG009	Phase 1 - Newly Diagnosed GBM / GS- Level 5	Mycophenolate mofetil; radiation therapy; temozolomide Temozolomide: 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. Mycophenolate Mofetil: 2000mg orally twice daily, one week prior to and concurrent with RT and cyclic chemotherapy with temozolomide. Radiation Therapy: 60 Gy in 30 fractions
BG010	Total	Total of all reporting groups

Units	Counts
Participants	BG0002 BG0012 BG0022 BG0032 BG0043 BG0054 BG00619 BG0074 BG00811 BG00916 BG01065

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

only phase 0 subjects were analyzed

Posted

Median

Full Range

nmol/g

At 1 week

ID	Title	Description
OG000	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 2	Mycophenolate mofetil Mycophenolate Mofetil: 500mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
OG001	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 3	Mycophenolate mofetil Mycophenolate Mofetil: 1000mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
OG002	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 4	Mycophenolate mofetil Mycophenolate Mofetil: 1500mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
OG003	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 5	Mycophenolate mofetil Mycophenolate Mofetil: 2000mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
OG004	Phase 1 - Recurrent GBM / GS - Level 3	Mycophenolate mofetil; radiation therapy Radiation Therapy: 40.5 Gy in 15 fractions Mycophenolate Mofetil: 1000mg orally twice daily, one week prior to and concurrent with RT.
OG005	Phase 1 - Recurrent GBM / GS - Level 4	Mycophenolate mofetil; radiation therapy Radiation Therapy: 40.5 Gy in 15 fractions Mycophenolate Mofetil: 1500mg orally twice daily, one week prior to and concurrent with RT.
OG006	Phase 1 - Recurrent GBM / GS - Level 5	Mycophenolate mofetil; radiation therapy Radiation Therapy: 40.5 Gy in 15 fractions Mycophenolate Mofetil: 2000mg orally twice daily, one week prior to and concurrent with RT.
OG007	Phase 1 - Newly Diagnosed GBM / GS - Level 3	Mycophenolate mofetil; radiation therapy; temozolomide Temozolomide: 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. Mycophenolate Mofetil: 1000mg orally twice daily, one week prior to and concurrent with RT and cyclic chemotherapy with temozolomide. Radiation Therapy: 60 Gy in 30 fractions
OG008	Phase 1 - Newly Diagnosed GBM / GS- Level 4	Mycophenolate mofetil; radiation therapy; temozolomide Temozolomide: 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. Mycophenolate Mofetil: 1500mg orally twice daily, one week prior to and concurrent with RT and cyclic chemotherapy with temozolomide. Radiation Therapy: 60 Gy in 30 fractions
OG009	Phase 1 - Newly Diagnosed GBM / GS- Level 5	Mycophenolate mofetil; radiation therapy; temozolomide Temozolomide: 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. Mycophenolate Mofetil: 2000mg orally twice daily, one week prior to and concurrent with RT and cyclic chemotherapy with temozolomide. Radiation Therapy: 60 Gy in 30 fractions

Units	Counts
Participants	OG0002 OG0012 OG0022 OG003

Title	Denominators	Categories
Enhancing Tumor	ParticipantsOG0002 ParticipantsOG0012 ParticipantsOG0022 ParticipantsOG003

Primary

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.

Only phase 1 recurrent subjects reported

Posted

Number

number of patients reporting a DLT

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

ID	Title	Description
OG000	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 2	Mycophenolate mofetil Mycophenolate Mofetil: 500mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
OG001	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 3	Mycophenolate mofetil Mycophenolate Mofetil: 1000mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
OG002	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 4

Primary

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.

Only Phase 1 newly diagnosed subjects analyzed

Posted

Number

number of patients reporting a DLT

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

ID	Title	Description
OG000	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 2	Mycophenolate mofetil Mycophenolate Mofetil: 500mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
OG001	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 3	Mycophenolate mofetil Mycophenolate Mofetil: 1000mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
OG002	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 4

Primary

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.

Only phase 1 newly diagnosed subjects analyzed

Posted

Number

number of patients reporting a DLT

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

ID	Title	Description
OG000	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 2	Mycophenolate mofetil Mycophenolate Mofetil: 500mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
OG001	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 3	Mycophenolate mofetil Mycophenolate Mofetil: 1000mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care
OG002

Secondary

Concentrations of Guanosine Triphosphate (GTP) in Tumor Tissue in Phase 0 Participants

The concentrations of GTP in tumor tissue, measured by mass spectrometry on a continuous scale.

This measure includes all phase 0 participants.

Not Posted

After one week of MMF administration

Participants

Secondary

Adverse Events Associated With Treatment in All Phase 1 Participants

Toxicities at each dose level will be tabulated, categorized by grade and attribution.

This measure includes all phase 1 participants.

Not Posted

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

Participants

Secondary

Adverse Events Associated With Treatment in Newly Diagnosed Phase 1 Participants

Toxicities at each dose level will be tabulated, categorized by grade and attribution.

This measure includes only newly diagnosed phase 1 participants.

Not Posted

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

Participants

Secondary

Overall Response Rate in Phase 1 Participants With Recurrent GBM/GS

Determined by modified Response Assessment for Neuro-Oncology (mRANO) criteria. The number and proportion of patients with progressive disease, stable disease, partial and complete response will be calculated for each dose level and overall.

This measure includes only phase 1 participants with recurrent GBM/GS.

Not Posted

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

Participants

Secondary

Median Progression Free Survival (PFS) in Phase 1 Participants With Recurrent GBM/GS

PFS defined as time from date of registration to the date of documented progressive disease, other disease related therapy or death. Determined by mRANO criteria.

This measure includes only phase 1 participants with recurrent GBM/GS.

Not Posted

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

Participants

Secondary

Median Freedom From Local Progression (FFLP) in Phase 1 Participants With Recurrent GBM/GS

FFLP defined as time from date of registration to the date of documented local progressive disease. Determined by mRANO criteria.

This measure includes only phase 1 participants with recurrent GBM/GS.

Not Posted

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

Participants

Secondary

Median Overall Survival (OS) in Phase 1 Participants With Recurrent GBM/GS

OS defined as time from date of registration to date of death or last follow up. Determined by Kaplan Meier method.

This measure includes only phase 1 participants with recurrent GBM/GS.

Not Posted

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

Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 2	Mycophenolate mofetil Mycophenolate Mofetil: 500mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care	1	2	1	2	2	2
EG001	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 3	Mycophenolate mofetil Mycophenolate Mofetil: 1000mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care	1	2	0	2	0	2
EG002	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 4	Mycophenolate mofetil Mycophenolate Mofetil: 1500mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care	0	2	0	2	2	2
EG003	Phase 0 - Recurrent Glioblastoma (GBM) / Gliosarcoma (GS) - Level 5	Mycophenolate mofetil Mycophenolate Mofetil: 2000mg orally twice daily, one week prior to re-resection Re-resection (as part of standard of care): Re-resection or biopsy of tumor as part of standard of care	1	2	0	2	2	2
EG004	Phase 1 - Recurrent GBM / GS - Level 3	Mycophenolate mofetil; radiation therapy Radiation Therapy: 40.5 Gy in 15 fractions Mycophenolate Mofetil: 1000mg orally twice daily, one week prior to and concurrent with RT.	2	3	0	3	3	3
EG005	Phase 1 - Recurrent GBM / GS - Level 4	Mycophenolate mofetil; radiation therapy Radiation Therapy: 40.5 Gy in 15 fractions Mycophenolate Mofetil: 1500mg orally twice daily, one week prior to and concurrent with RT.	4	4	2	4	4	4
EG006	Phase 1 - Recurrent GBM / GS - Level 5	Mycophenolate mofetil; radiation therapy Radiation Therapy: 40.5 Gy in 15 fractions Mycophenolate Mofetil: 2000mg orally twice daily, one week prior to and concurrent with RT.	12	19	2	19	16	19
EG007	Phase 1 - Newly Diagnosed GBM / GS - Level 3	Mycophenolate mofetil; radiation therapy; temozolomide Temozolomide: 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. Mycophenolate Mofetil: 1000mg orally twice daily, one week prior to and concurrent with RT and cyclic chemotherapy with temozolomide. Radiation Therapy: 60 Gy in 30 fractions	2	4	1	4	4	4
EG008	Phase 1 - Newly Diagnosed GBM / GS- Level 4	Mycophenolate mofetil; radiation therapy; temozolomide Temozolomide: 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. Mycophenolate Mofetil: 1500mg orally twice daily, one week prior to and concurrent with RT and cyclic chemotherapy with temozolomide. Radiation Therapy: 60 Gy in 30 fractions	8	11	4	11	10	11
EG009	Phase 1 - Newly Diagnosed GBM / GS- Level 5	Mycophenolate mofetil; radiation therapy; temozolomide Temozolomide: 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. Mycophenolate Mofetil: 2000mg orally twice daily, one week prior to and concurrent with RT and cyclic chemotherapy with temozolomide. Radiation Therapy: 60 Gy in 30 fractions	11	16	9	16	16	16

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Aspiration	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG0030 events0 affected2 at risk EG004
Dysphasia	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Encephalopathy	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Intracranial hemorrhage	Blood and lymphatic system disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Muscle weakness right-sided	Musculoskeletal and connective tissue disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Aortic injury	Blood and lymphatic system disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Cerebrospinal fluid leakage	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Fall	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Fatigue	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Hypokalemia	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Nausea	Gastrointestinal disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Left sided hemiparesis	Nervous system disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Platelet count decreased	Investigations	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Seizure	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Suicide attempt	Psychiatric disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cushingoid	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG0030 events0 affected2 at risk EG004
Delirium	Psychiatric disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Depression	Psychiatric disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0021 events1 affected2 at risk EG003
Fatigue	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0002 events2 affected2 at risk EG0010 events0 affected2 at risk EG0021 events1 affected2 at risk EG003
Gastroesophageal reflux disease	Gastrointestinal disorders	CTCAE (5.0)	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	CTCAE (5.0)	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Headache	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0021 events1 affected2 at risk EG003
Insomnia	Psychiatric disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0021 events1 affected2 at risk EG003
Memory impairment	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Paresthesia	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Seizure	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Sepsis	Infections and infestations	CTCAE (5.0)	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Sinus bradycardia	Cardiac disorders	CTCAE (5.0)	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Syncope	Cardiac disorders	CTCAE (5.0)	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Thromboembolic event	Blood and lymphatic system disorders	CTCAE (5.0)	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Urinary tract infection	Infections and infestations	CTCAE (5.0)	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Alopecia	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Diarrhea	Gastrointestinal disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Dizziness	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Dysphasia	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Gait disturbance	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Intracranial hemorrhage	Blood and lymphatic system disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Lymphocyte count decreased	Investigations	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Nausea	Gastrointestinal disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Vomiting	Gastrointestinal disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Alanine aminotransferase increased	Investigations	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Anorexia	Psychiatric disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Anxiety	Psychiatric disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Arthralgia	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Aspartate aminotransferase increased	Investigations	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Chills	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Cognitive disturbance	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Confusion	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Constipation	Gastrointestinal disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Dysgeusia	Gastrointestinal disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Dyspepsia	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Dysphasia	Gastrointestinal disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Neutrophil count decreased	Investigations	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Pain in extremity	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Platelet count decreased	Investigations	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Scalp pain	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Tremor	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Upper respiratory infection	Infections and infestations	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Weight loss	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
White blood cell decreased	Investigations	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Dry Mouth	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Urinary frequency	Renal and urinary disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Edema limbs	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Fall	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Dysesthesia	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Facial muscle weakness	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Shingles	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Stomach pain	Gastrointestinal disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Tinnitus	Ear and labyrinth disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Weight gain	Metabolism and nutrition disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Agitation	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Bullous dermatitis	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Concentration impairment	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Eye infection	Eye disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Hiccups	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Retinal detachment	Eye disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Sinusitis	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Thrush	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Anemia	Infections and infestations	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Dysphagia	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Dry eye	Eye disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Gallbladder pain	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Hyperglycemia	Infections and infestations	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Hypoglycemia	Investigations	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Malaise	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Mucositis oral	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Abdominal pain	Gastrointestinal disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Arthritis	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Ataxia	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Blurred vision	Eye disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Bronchospasm	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Hydrocephalus	General disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Sinus tachycardia	Cardiac disorders	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003
Skin infection	Infections and infestations	CTCAE (5.0)	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected2 at risk EG0020 events0 affected2 at risk EG003

ID	Term
D001254	Astrocytoma
D005910	Glioma
D018302	Neoplasms, Neuroepithelial
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009375	Neoplasms, Glandular and Epithelial
D009380	Neoplasms, Nerve Tissue

ID	Term
D002208	Caproates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D005227	Fatty Acids
D008055	Lipids
D013812	Therapeutics
D003606	Dacarbazine
D014226	Triazenes
D007093	Imidazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

ID	Term
D009173	Mycophenolic Acid
D011878	Radiotherapy
D000077204	Temozolomide