A Phase II Clinical Trial Evaluating the Combination of Olaparib and Temozolomide for the Treatment of Advanced Uterine Leiomyosarcoma

Exclusion Criteria

• •Patients must be able to have temozolomide provided as a standard of care medication.
• •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.