Testing Ramipril to Prevent Memory Loss in People With Glioblastoma

Inclusion Criteria:

• Histologically proven diagnosis of glioblastoma or gliosarcoma (World HealthOrganization [WHO] grade IV) obtained at the time of a partial or gross totalresection of the tumor. Patients who undergo a stereotactic needle biopsy alone arenot eligible.

• The tumor must have a supratentorial component.

• History/physical examination within 14 days prior to enrollment.

• The patient must have recovered from the effects of surgery, postoperativeinfection, and other complications before enrollment

• Patient planning to receive brain RT, and concurrent and adjuvant temozolomidechemotherapy for six weeks as per standard of care therapy. Use of the Optune® (alsoknown as Tumor Treating Fields or TTFields) device is allowed at providerdiscretion, but must begin after the Month 1 Post RT (10 week [wk])Neurocognitive-PRO assessment.

• Study drug (Ramipril) must be given >= 21 days and ≤ 42 days after surgery.

• All available brain magnetic resonance imaging (MRI) or computed tomography (CT)imaging reports from surgery to study completion must be submitted. This includesany post-operative or pre-radiation scan reports.

• Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2

• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (obtained within 14 days priorto enrollment)

• Platelets >= 100,000 cells/mm^3 (obtained within 14 days prior to enrollment)

• Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention toachieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable) (obtained within 14 days priorto enrollment)

• Blood urea nitrogen (BUN) =< 30 mg/dl within 14 days prior to enrollment

• Creatinine =< 1.7 mg/dl within 14 days prior to enrollment

• Total bilirubin =< 2.0 mg/dl within 14 days prior to enrollment

• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3 x normal rangewithin 14 days prior to enrollment

• Patient must provide study specific informed consent prior to study entry

• Baseline potassium level <5.0 mEq/L. High potassium values that are thought to be aresult of sample hemolysis may be repeated to determine an accurate potassium leveland to determine potential study eligibility. Likewise high potassium values thoughtto be a result of potassium supplementation may be repeated at an appropriate time (5 half-lives after supplement discontinuation) to determine potential studyeligibility.

Patient must be able to complete neurocognitive tests in the English language

• Women of childbearing potential and male participants must practice adequatecontraception

• For females of child-bearing potential, negative serum or urine pregnancy testwithin 14 days of enrollment

• Local site must be follow the standard GBM radiation treatment dosimetry plan

• For patients who will be treated with the Optune® device in addition to standard ofcare radiation plus concurrent and adjuvant temozolomide, the following inclusioncriteria also apply:

• Patients must have only a supratentorial glioblastoma

• The treating physician must be a qualified provider having successfully completedthe training course provided by Novocure, the device manufacturer

• Patients with prior malignancies if all treatment for that malignancy was completedat least 2 years before registration and the patient has no evidence of disease.

Exclusion Criteria:

• Prior allergic reaction or intolerance to angiotensin-converting-enzyme (ACE)inhibitor

• Hypotension (< 110 mg Hg systolic) at the time of enrollment

• Renal insufficiency with creatinine clearance of < 40 ml/min (at time of enrollment)

• Solitary kidney or known renal artery stenosis

• Current ACE inhibitor or angiotensin receptor blocker use. Patients can come off ACEinhibitors or angiotensin receptor blockers for 1 week to be eligible for thisstudy.

• Prior invasive malignancy (except for non-melanomatous skin cancer) unless diseasefree for ≥ 2 years. (For example, carcinoma in situ of the breast, oral cavity, andcervix are all permissible).

• Recurrent or multifocal malignant gliomas

• Metastases detected below the tentorium or beyond the cranial vault

• Prior chemotherapy or radiosensitizers for cancers of the head and neck region; notethat prior chemotherapy for a different cancer is allowable, except priortemozolomide. Prior use of Gliadel wafers or any other intratumoral or intracavitarytreatment are not permitted.

• Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting inoverlap of radiation fields.

• Severe active co-morbidity, defined as follows:

• Acute bacterial or fungal infection requiring intravenous antibiotics at the time ofenrollment

• Chronic obstructive pulmonary disease exacerbation or other respiratory illnessrequiring hospitalization or precluding study therapy at the time of enrollment.

• Known HIV positivity or acquired immune deficiency syndrome (AIDS) based uponcurrent CDC definition; note, however, that HIV testing is not required for entryinto this protocol. The need to exclude patients with AIDS from this protocol isnecessary because the treatments involved in this protocol may be significantlyimmunosuppressive.

• Active connective tissue disorders, such as lupus or scleroderma, that in theopinion of the treating physician may put the patient at high risk for radiationtoxicity.

• Any other major medical illnesses or psychiatric impairments that in theinvestigator's opinion will prevent administration or completion of protocoltherapy.

• Pregnancy or women of childbearing potential and men who are sexually active and notwilling/able to use medically acceptable forms of contraception; this exclusion isnecessary because the treatment involved in this study may be significantlyteratogenic.

• Patients treated on any other therapeutic clinical protocols within 30 days prior tostudy entry or during participation in the study unless they involve standard ofcare or over the counter therapies or do not involve a drug therapy.

• Patients planning to receive therapeutic antitumor agents (excluding use of theTumor Treating Fields (TTFields or Optune®) device after the Month 1 Post RT (10 wk)Neurocognitive-PRO assessment.) in addition to standard radiation and concurrent andadjuvant temozolomide are not eligible to participate in this study.

• Patients with impaired decision-making capacity; this exclusion is necessary becausesuch patients may not be able to adequately give informed consent.

• Pregnant or lactating women, due to possible adverse effect on the developing fetusor infant due to study drug.

• For patients who will be treated with the Optune® device in addition to standard ofcare radiation plus concurrent and adjuvant temozolomide, the following exclusioncriteria also apply:

• Optune® is not permitted in patients who have an active implanted medical device,skull defect (such as, missing bone with no replacement) or bullet fragments.Examples of active electronic devices include deep brain stimulators, spinal cordstimulators, vagus nerve stimulators, pacemakers, defibrillators, and programmaticshunts.

• Optune® is not permitted in patients who are known to be sensitive to conductivehydrogels. Examples of conductive hydrogels are gels used on electrocardiogram (ECG)stickers or transcutaneous electrical nerve stimulation (TENS) electrodes.

• Patients being treated with Memantine, Donepezil, and/or medications prescribed toenhance cognition.