Clinical Research Directory

Inclusion Criteria: * Patients must have histologically documented LMS of uterine origin. Pathology review and confirmation of diagnosis will occur at the site enrolling the patient on this study. * Patients must have locally advanced and unresectable or metastatic disease. * Patients must have disease which is measurable at study entry according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Additionally, patients must have a site of disease deemed accessible for biopsy at no or minimal risk to the patient (including through the use of image-guidance). If there are questions regarding the feasibility of biopsy, the case should be reviewed with interventional radiology or the appropriate department at the study site prior to registration. * Patients must have had prior progression on, or intolerance to, at least one line of systemic therapy for advanced LMS. Adjuvant therapy administered after curative resection will not qualify as prior treatment. There is no upper limit on the number of prior therapies received. * Patients must be \>= 18 years of age. Uterine LMS affects older adults and is rarely encountered in children and adolescents. * Patients must demonstrate an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of =\< 2 (Karnofsky \>= 50%). * Absolute neutrophil count \>= 1,500/mcL (measured within 14 days prior to administration of study treatment). * Hemoglobin \>= 9 g/dL (without transfusion of packed red blood cells within the past 28 days) (measured within 14 days prior to administration of study treatment). * Platelets \>= 100,000/mcL (measured within 14 days prior to administration of study treatment). * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (measured within 14 days prior to administration of study treatment). * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (measured within 14 days prior to administration of study treatment). * Glomerular filtration rate (GFR) \>= 51 mL/min, based on a 24-hour urine test for creatinine clearance or estimated using the Cockcroft-Gault equation (measured within 14 days prior to administration of study treatment). * If patients have evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of hepatitis B surface antigen \[HBsAg\]) are eligible. * If patients have a history of hepatitis C virus (HCV) infection, they must be treated with undetectable HCV viral load (polymerase chain reaction is negative for HCV ribonucleic acid \[RNA\]). * Patients must be postmenopausal or have evidence of non-childbearing status, OR, for women of childbearing potential, must have a negative urine or serum pregnancy test within 28 days of study treatment and confirmed again on day 1 prior to study treatment. * Postmenopausal is defined as: * Amenorrheic for \>= 1 year following cessation of exogenous hormonal treatments * Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50 * Radiation-induced oophorectomy with last menses \> 1 year ago * Chemotherapy-induced menopause with \> 1 year interval since last menses * Surgical sterilization (bilateral oophorectomy or hysterectomy). * Patients and their partners, if sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination throughout the period of taking study treatment and for 3 months after the last dose of study drug(s) to prevent pregnancy in the study patient or partner. * Patients must be able to swallow orally administered medication. * Patients must have a life expectancy \>= 16 weeks. * Patients must be able to understand and be willing to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) will be eligible if they have a close caregiver or legally authorized representative (LAR) available to assist them. * Patients must be willing and able to comply with the protocol for the duration of the study, including undergoing treatment and attending scheduled visits and examinations. * Patients with human immunodeficiency virus (HIV) infection may be enrolled on this study provided: (a) they are on a stable regimen of highly active anti-retroviral therapy (HAART) with no medications otherwise prohibited by this protocol (e.g. drug-drug interactions) and (b) require no concurrent antibiotics or antifungals for the prevention of opportunistic infections and (c) have a CD4 count above 250 cell/mcL and an undetectable viral load on standard polymerase chain reaction (PCR)-based tests within 1 month of initiation of study treatment. Other patients with clinically significant immunosuppression, e.g. organ transplant patients, are not eligible. If clarification is needed, this may be discussed with the medical monitor. * Patients must be able to have temozolomide provided as a standard of care medication. Exclusion Criteria: * Patients must not have had any previous treatment with any poly(adenosine diphosphate\[ADP\]-ribose) polymerase (PARP) inhibitors, including olaparib, or prior treatment with dacarbazine and/or temozolomide. * Patients must have recovered from adverse events due to prior anti-cancer therapy (i.e., may not have residual toxicities \> grade 1 or above baseline), excluding alopecia. Patients who have endocrinopathies associated with prior immunotherapy treatment but which are controlled with replacement therapy are eligible. * Prior to initiating study treatment, at least 28 days must have elapsed from the last dose of systemic anti-cancer treatment (cytotoxic, biologic or immunotherapeutic) or radiation therapy (except for palliative radiation, in which case a 14-day washout applies). * Patients must not have had major surgery within 2 weeks of starting study treatment and must have recovered from any effects of any major surgery that occurred \> 2 weeks before starting study treatment. * Patients must not be receiving any other investigational agent. * Patients must not have been diagnosed with another malignancy unless curatively treated with no evidence of disease for \>= 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), or any other malignant condition considered indolent and unlikely to require active therapy. * Patients must not have myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or bone marrow biopsy findings consistent with MDS and/or AML. * Patients must not have active central nervous system (CNS) or leptomeningeal disease at the time of enrollment. Patients with a history of such disease previously treated with curative intent (such as with surgery or radiation) that have not progressed on subsequent imaging, have been clinically asymptomatic, and have not received systemic corticosteroids for at least 28 days, are eligible. * Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib or TMZ or any of the excipients of any study product. * Patients must refrain from concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period for strong or moderate CYP3A inhibitors prior to starting olaparib is 2 weeks. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. * Patients must refrain from concomitant use of known strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period for strong or moderate CYP3A inducers prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. * Patients must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan, or psychiatric illness that would limit compliance with study requirements. * Pregnant women are excluded from this study because olaparib is a PARP inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib, breastfeeding should be discontinued if the mother is treated with olaparib. These potential risks may also apply to other agents used in this study. * Patients must not have gastrointestinal disorders likely to interfere with absorption of the study medication. * Patients must not have had involvement in the planning and/or conduct of the study.