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Peposertib and Radiation Therapy, Followed by Temozolomide for the Treatment of Patients With Newly Diagnosed MGMT Unmethylated Glioblastoma or Gliosarcoma

Primary Purpose

Glioblastoma, Gliosarcoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Peposertib
Radiation Therapy
Resection
Temozolomide
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Signed informed consent form (ICF)
  • Ability and willingness to comply with the requirement of the study protocol
  • Histologically confirmed World Health Organization (WHO) grade IV glioma (GBM) or gliosarcoma, IDH wild-type
  • Documentation of MGMT unmethylated GBM per testing at any Clinical Laboratory Improvement Amendment (CLIA) certified laboratory
  • Patients must have undergone brain surgery or biopsy and must not have had any further treatments following surgery
  • Have Karnofsky performance status (KPS) of >= 60 or Eastern Cooperative Oncology Group (ECOG) =< 2
  • A baseline magnetic resonance imaging (MRI) of brain obtained no more than 14 days prior to study enrollment on a stable or tapering dose of steroids no greater than 4 mg a day of dexamethasone (or equivalent dose of other steroids) for at least 3 days
  • Patients must start treatment within 8 weeks of last brain surgical procedure (biopsy or resection)
  • Absolute neutrophil count (ANC) >= 1,500 /mcL (within 14 days prior to day 1 of the study)
  • Platelets >= 100,000/mcL (within 14 days prior to day 1 of the study)
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (within 14 days prior to day 1 of the study)
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN (within 14 days prior to day 1 of the study)

    • Creatinine clearance should be calculated per institutional standard
  • Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 x ULN (within 14 days prior to day 1 of the study)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (within 14 days prior to day 1 of the study)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN (within 14 days prior to day 1 of the study)
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (within 14 days prior to day 1 of the study)
  • Have provided tissue from an archival tissue sample
  • Female subjects of childbearing potential should have a negative serum pregnancy test within 14 days of day 1 of the study
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile

    • Female subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects should agree to use an adequate method of contraception during the course of the study
  • STAGE I: In the case stage I patients need resection as determined by the treating physicians during or after completion of radiation therapy (RT) and that pathology of resected lesion is not consistent with recurrent GBM, the patient can continue on the study (complete 6 weeks of RT + M3814) if deemed appropriate by the treating physicians. The tissue obtained in such circumstances will be analyzed as in Stage II subjects. However, these cases will not count towards the 5 patients who will be enrolled during Stage II. These patients will contribute to the correlative endpoints detailed above and ORR, OS, and PFS as Stage II patients
  • STAGE II: Patients meet above criteria, would benefit from further non-urgent surgical resection of at least one enhancing lesion per the treating physician, and would provide consent to undergo surgery after treatment with RT and M3814

Exclusion Criteria:

  • Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery. Prior treatment with Gliadel wafers and laser interstitial thermal therapy (LITT) will be excluded. Active treatment with the tumor treating filed devices such as Optune will be excluded
  • Currently participating or previously participated in any other newly diagnosed GBM therapeutic trials
  • History of MGMT methylated status performed at any CLIA certified laboratory
  • Any serious medical condition that interferes with adherence to study procedures
  • Malignancies other than the disease under study within 5 years prior to day 1 of the study, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai stage 0, prostate cancer with Gleason score =< 6, and prostate-specific antigen [PSA] =< 10 mg/mL, etc)
  • Has known disease in the posterior fossa, gliomatous meningitis, extracranial disease or multicentric enhancing disease. Multicentric disease is defined as discrete sites of contrast enhancing disease without contiguous T2/fluid-attenuated inversion recovery (FLAIR) abnormality that require distinct radiotherapy ports. Satellite lesions that are associated with a contiguous area of T2/FLAIR abnormality as the main lesion(s) and that are encompassed within the same radiotherapy port as the main lesion(s) are permitted
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating physician
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the screening visit
  • Contraindication for undergoing MRIs
  • Inability to comply with study and follow-up procedures
  • Signs or symptoms of infection, received oral or intravenous (IV) antibiotics within 2 weeks prior to day 1 of the study

    • Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
  • History of human immunodeficiency virus (HIV) infection
  • Administration of a live, attenuated vaccine within 4 weeks before day 1 of the study or anticipation that such a live, attenuated vaccine will be required during the study
  • Influenza vaccination can be given. Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to day 1 of the study or at any time during the study and for 5 months after completion of adjuvant temozolomide (TMZ)
  • History of long QT syndrome
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of M3814 or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • Anticipation of need for a major surgical procedure during the course of the study (excluding patients in Stage II with planed non-urgent neuro-surgical resection)
  • Subjects at increased risk for radiation toxicities, such as known active collagen vascular disease (example; scleroderma, Sjogren's disease, etc) or other inherited radiation hypersensitivity syndromes (example; Gorlin syndrome, Fanconi anemia, ataxia-telangiectasia, etc.)
  • Active difficulty swallowing, malabsorption or other chronic gastrointestinal disease or conditions (including pancreas deficiency requiring Creon therapy) that may hamper compliance and/or absorption of M3814
  • Patients may not receive concomitant chemotherapy, immunotherapy, or radiotherapy (other than as pertained to standard of care for GBM) while patients are on study
  • Prior treatment with DNA damage response inhibitors (including inhibitors of PARP, ATR, WEE)
  • Subjects currently receiving or unable to stop using medications or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A, CYP2C19, CYP2C9 and/or P glycoprotein (P-gp) (CYP and/P-gp must stop at least 1 week before treatment with M3814 for inhibitors and 3 weeks before treatment with M3814 for inducers) or drugs mainly metabolized by CYP3A, CYP2C19, CYP2C9 with a narrow therapeutic index (must stop at least 1 day prior). In addition concomitant use of H2 blockers of proton pump inhibitors (PPIs) is prohibited. Patients must stop H2 blockers and PPIs 4 days prior to the first treatment. Calcium carbonate use is acceptable
  • STAGE II: Patients who are status post (s/p) gross total resection with no remaining disease available for resection or tumor remaining in a region of the brain not amenable to resection

Sites / Locations

  • M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Stage I (Peposertib, Radiation therapy, Temozolomide)

Stage II (Peposertib, Radiation, Temozolomide, Surgery)

Arm Description

CONCURRENT: Patients undergo standard of care radiation therapy daily (Monday-Friday) for 30 fractions. Patients also receive Peposertib PO on each day of radiation therapy and given 1-2 hours before each treatment fraction. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT: Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

CONCURRENT: Patients receive Peposertib and undergo standard of care radiation therapy as in Stage I. Within 1-14 days after the completion of radiation therapy, patients undergo surgical resection. ADJUVANT: Patients receive temozolomide as in Stage I.

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) (Stage I)
Will employ the Bayesian optimal interval to find the MTD.
Ability of Peposertib (M3814) to cross the blood brain barrier (Stage II)
Ability of the investigational drug to cross the blood brain barrier will be tested by measuring concentration of the drug within the blood and the resected brain tumor tissue. This will be correlated with biomarkers of deoxyribonucleic acid (DNA) damage in brain tumor tissue, blood, and hair follicle.

Secondary Outcome Measures

Dose-limiting toxicities (DLT) (Stage I)
A DLT is defined as a clinically significant adverse event considered at least possibly related to M3814 in combination with radiation during the first 10 weeks of study treatment (4 weeks after completion of radiation and DNA damage response [DDR] inhibitors) for both stage I and stage II patients.
Overall response rate (Stage I)
Median progression-free survival (Stage I)
Median overall survival (Stage I)
Overall response rate (Stage II)
Median progression-free survival (Stage II)
Progression-free survival will be evaluated using the Kaplan-Meier product-limit survival curve methodology and will be compared to historical controls. Median progression free survival will be estimated using Kaplan-Meier estimates and associated two-sided 95% confidence intervals.
Median overall survival (Stage II)
Overall survival will be evaluated using the Kaplan-Meier product-limit survival curve methodology and will be compared to historical controls.

Full Information

First Posted
August 10, 2020
Last Updated
August 29, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04555577
Brief Title
Peposertib and Radiation Therapy, Followed by Temozolomide for the Treatment of Patients With Newly Diagnosed MGMT Unmethylated Glioblastoma or Gliosarcoma
Official Title
Phase I Trial of DNA-PK Inhibitor (M3814) in Combination With Radiation and Adjuvant Temozolomide in Newly Diagnosed MGMT Unmethylated Glioblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 20, 2020 (Actual)
Primary Completion Date
October 30, 2023 (Anticipated)
Study Completion Date
October 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase I trial investigates the side effects and best dose of Peposertib, and to see how well it works in combination with radiation therapy in treating patients with newly diagnosed MGMT unmethylated glioblastoma or gliosarcoma. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Peposertib may further stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Peposertib with radiation therapy may work better than radiation therapy alone in treating patients with glioblastoma or gliosarcoma.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of Peposertib (M3814) in combination with standard of care radiation dose (60 Gy, 2 Gy/fraction over 6 weeks) in patients with newly diagnosed MGMT unmethylated glioblastoma (GBM). (Stage I) II. To determine the ability of M3814 to cross the blood brain barrier and to evaluate their pharmacodynamic properties in resected tissue. (Stage II) SECONDARY AND EXPLORATORY OBJECTIVES: I. To evaluate the dose limiting toxicities (DLT). (Stage I) (Secondary Objective) II. To determine the overall response rate (ORR), median progression free survival (mPFS) and median overall survival (mOS) of M3814 in combination with radiation. (Stage I) (Secondary Objective) II. To determine the overall response rate (ORR), median progression free survival (mPFS) and median overall survival (mOS) of M3814 in combination with radiation. (Stage II) (Exploratory Objective) CORRELATIVE OBJECTIVES: I. To evaluate pharmacodynamic properties of M3814. II. To assess the alterations in tumor immune microenvironment as a result of deoxyribonucleic acid (DNA)-dependent protein kinase (DNA-PK) inhibition. OUTLINE: This is a dose-escalation study of Peposertib. Patients are assigned to 1 of 2 stages. STAGE I (CONCURRENT): Patients undergo standard of care radiation therapy daily (Monday-Friday) for 30 fractions. Patients also receive Peposertib orally (PO) on each day of radiation therapy and given 1-2 hours before each treatment fraction. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. STAGE I (ADJUVANT): Patients receive temozolomide PO once daily (QD) on days 1-5. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. STAGE II (CONCURRENT): Patients receive Peposertib and undergo standard of care radiation therapy as in Stage I. Within 1-14 days after the completion of radiation therapy, patients undergo surgical resection. STAGE II (ADJUVANT): Patients receive temozolomide as in Stage I. After completion of study treatment, patients are followed up every 3 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Gliosarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
29 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Stage I (Peposertib, Radiation therapy, Temozolomide)
Arm Type
Experimental
Arm Description
CONCURRENT: Patients undergo standard of care radiation therapy daily (Monday-Friday) for 30 fractions. Patients also receive Peposertib PO on each day of radiation therapy and given 1-2 hours before each treatment fraction. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT: Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Arm Title
Stage II (Peposertib, Radiation, Temozolomide, Surgery)
Arm Type
Experimental
Arm Description
CONCURRENT: Patients receive Peposertib and undergo standard of care radiation therapy as in Stage I. Within 1-14 days after the completion of radiation therapy, patients undergo surgical resection. ADJUVANT: Patients receive temozolomide as in Stage I.
Intervention Type
Drug
Intervention Name(s)
Peposertib
Intervention Description
Given PO
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Other Intervention Name(s)
Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
Intervention Description
Undergo radiation therapy
Intervention Type
Procedure
Intervention Name(s)
Resection
Other Intervention Name(s)
Surgical Resection
Intervention Description
Undergo surgical resection
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) (Stage I)
Description
Will employ the Bayesian optimal interval to find the MTD.
Time Frame
Within the first 10 weeks of study treatment
Title
Ability of Peposertib (M3814) to cross the blood brain barrier (Stage II)
Description
Ability of the investigational drug to cross the blood brain barrier will be tested by measuring concentration of the drug within the blood and the resected brain tumor tissue. This will be correlated with biomarkers of deoxyribonucleic acid (DNA) damage in brain tumor tissue, blood, and hair follicle.
Time Frame
At 1, 2, and 4 hours after drug administration on fraction day 1 and at pre-dose and 1, 2, and 4 hours after drug administration on fraction day 10
Secondary Outcome Measure Information:
Title
Dose-limiting toxicities (DLT) (Stage I)
Description
A DLT is defined as a clinically significant adverse event considered at least possibly related to M3814 in combination with radiation during the first 10 weeks of study treatment (4 weeks after completion of radiation and DNA damage response [DDR] inhibitors) for both stage I and stage II patients.
Time Frame
Within the first 10 weeks of study treatment
Title
Overall response rate (Stage I)
Time Frame
Up to 3 years
Title
Median progression-free survival (Stage I)
Time Frame
From study enrollment until time of first occurrence of disease progression, relapse, or death due to disease, assessed up to 3 years
Title
Median overall survival (Stage I)
Time Frame
Up to 3 years
Title
Overall response rate (Stage II)
Time Frame
Up to 3 years
Title
Median progression-free survival (Stage II)
Description
Progression-free survival will be evaluated using the Kaplan-Meier product-limit survival curve methodology and will be compared to historical controls. Median progression free survival will be estimated using Kaplan-Meier estimates and associated two-sided 95% confidence intervals.
Time Frame
From study enrollment until time of first occurrence of disease progression, relapse, or death due to disease, assessed up to 3 years
Title
Median overall survival (Stage II)
Description
Overall survival will be evaluated using the Kaplan-Meier product-limit survival curve methodology and will be compared to historical controls.
Time Frame
Up to 3 years
Other Pre-specified Outcome Measures:
Title
Pharmacodynamic properties of M3814
Description
Blood and hair follicle will be obtained from stage I & II patients during the screening period, on days 8-12 of concurrent radiation and M3814, and on the last day of radiation and at disease progression. Logistic regression will be used to explore the correlations between response rates and correlative markers. Changes in correlative markers over time will be analyzed by Wilcoxon signed rank tests for pairs of times and linear mixed effects models more generally. Data graphs will be generated to visualize data distributions as well as relationships between variables.
Time Frame
Up to 3 years
Title
Alterations in tumor immune microenvironment
Description
Will assess the alterations in tumor immune microenvironment as a result of deoxyribonucleic acid-dependent protein kinase inhibition. Logistic regression will be used to explore the correlations between response rates and correlative markers. Changes in correlative markers over time will be analyzed by Wilcoxon signed rank tests for pairs of times and linear mixed effects models more generally. Data graphs will be generated to visualize data distributions as well as relationships between variables.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent form (ICF) Ability and willingness to comply with the requirement of the study protocol Histologically confirmed World Health Organization (WHO) grade IV glioma (GBM) or gliosarcoma, IDH wild-type Documentation of MGMT unmethylated GBM per testing at any Clinical Laboratory Improvement Amendment (CLIA) certified laboratory Patients must have undergone brain surgery or biopsy and must not have had any further treatments following surgery Have Karnofsky performance status (KPS) of >= 60 or Eastern Cooperative Oncology Group (ECOG) =< 2 A baseline magnetic resonance imaging (MRI) of brain obtained no more than 14 days prior to study enrollment on a stable or tapering dose of steroids no greater than 4 mg a day of dexamethasone (or equivalent dose of other steroids) for at least 3 days Patients must start treatment within 8 weeks of last brain surgical procedure (biopsy or resection) Absolute neutrophil count (ANC) >= 1,500 /mcL (within 14 days prior to day 1 of the study) Platelets >= 100,000/mcL (within 14 days prior to day 1 of the study) Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (within 14 days prior to day 1 of the study) Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN (within 14 days prior to day 1 of the study) Creatinine clearance should be calculated per institutional standard Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 x ULN (within 14 days prior to day 1 of the study) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (within 14 days prior to day 1 of the study) International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN (within 14 days prior to day 1 of the study) Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (within 14 days prior to day 1 of the study) Have provided tissue from an archival tissue sample Female subjects of childbearing potential should have a negative serum pregnancy test within 14 days of day 1 of the study Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile Female subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year Male subjects should agree to use an adequate method of contraception during the course of the study STAGE I: In the case stage I patients need resection as determined by the treating physicians during or after completion of radiation therapy (RT) and that pathology of resected lesion is not consistent with recurrent GBM, the patient can continue on the study (complete 6 weeks of RT + M3814) if deemed appropriate by the treating physicians. The tissue obtained in such circumstances will be analyzed as in Stage II subjects. However, these cases will not count towards the 5 patients who will be enrolled during Stage II. These patients will contribute to the correlative endpoints detailed above and ORR, OS, and PFS as Stage II patients STAGE II: Patients meet above criteria, would benefit from further non-urgent surgical resection of at least one enhancing lesion per the treating physician, and would provide consent to undergo surgery after treatment with RT and M3814 Exclusion Criteria: Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery. Prior treatment with Gliadel wafers and laser interstitial thermal therapy (LITT) will be excluded. Active treatment with the tumor treating filed devices such as Optune will be excluded Currently participating or previously participated in any other newly diagnosed GBM therapeutic trials History of MGMT methylated status performed at any CLIA certified laboratory Any serious medical condition that interferes with adherence to study procedures Malignancies other than the disease under study within 5 years prior to day 1 of the study, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai stage 0, prostate cancer with Gleason score =< 6, and prostate-specific antigen [PSA] =< 10 mg/mL, etc) Has known disease in the posterior fossa, gliomatous meningitis, extracranial disease or multicentric enhancing disease. Multicentric disease is defined as discrete sites of contrast enhancing disease without contiguous T2/fluid-attenuated inversion recovery (FLAIR) abnormality that require distinct radiotherapy ports. Satellite lesions that are associated with a contiguous area of T2/FLAIR abnormality as the main lesion(s) and that are encompassed within the same radiotherapy port as the main lesion(s) are permitted Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating physician Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the screening visit Contraindication for undergoing MRIs Inability to comply with study and follow-up procedures Signs or symptoms of infection, received oral or intravenous (IV) antibiotics within 2 weeks prior to day 1 of the study Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible History of human immunodeficiency virus (HIV) infection Administration of a live, attenuated vaccine within 4 weeks before day 1 of the study or anticipation that such a live, attenuated vaccine will be required during the study Influenza vaccination can be given. Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to day 1 of the study or at any time during the study and for 5 months after completion of adjuvant temozolomide (TMZ) History of long QT syndrome Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of M3814 or that may affect the interpretation of the results or render the patient at high risk from treatment complications Anticipation of need for a major surgical procedure during the course of the study (excluding patients in Stage II with planed non-urgent neuro-surgical resection) Subjects at increased risk for radiation toxicities, such as known active collagen vascular disease (example; scleroderma, Sjogren's disease, etc) or other inherited radiation hypersensitivity syndromes (example; Gorlin syndrome, Fanconi anemia, ataxia-telangiectasia, etc.) Active difficulty swallowing, malabsorption or other chronic gastrointestinal disease or conditions (including pancreas deficiency requiring Creon therapy) that may hamper compliance and/or absorption of M3814 Patients may not receive concomitant chemotherapy, immunotherapy, or radiotherapy (other than as pertained to standard of care for GBM) while patients are on study Prior treatment with DNA damage response inhibitors (including inhibitors of PARP, ATR, WEE) Subjects currently receiving or unable to stop using medications or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A, CYP2C19, CYP2C9 and/or P glycoprotein (P-gp) (CYP and/P-gp must stop at least 1 week before treatment with M3814 for inhibitors and 3 weeks before treatment with M3814 for inducers) or drugs mainly metabolized by CYP3A, CYP2C19, CYP2C9 with a narrow therapeutic index (must stop at least 1 day prior). In addition concomitant use of H2 blockers of proton pump inhibitors (PPIs) is prohibited. Patients must stop H2 blockers and PPIs 4 days prior to the first treatment. Calcium carbonate use is acceptable STAGE II: Patients who are status post (s/p) gross total resection with no remaining disease available for resection or tumor remaining in a region of the brain not amenable to resection
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nazanin Majd, MD
Phone
713-792-2883
Email
nkmajd@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nazanin Majd, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nazanin Majd, MD
Phone
713-792-2883
Email
nkmajd@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Nazanin Majd, MD

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center

Learn more about this trial

Peposertib and Radiation Therapy, Followed by Temozolomide for the Treatment of Patients With Newly Diagnosed MGMT Unmethylated Glioblastoma or Gliosarcoma

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