delayed initiation of olaparib maintenance therapy in platinum sensitive recurrent ovarian cancer

Conditions: Ovarian Cancer

Summary: the purpose of this study is to test if delaying the start of the olaparib until there is a rise in a tumor marker called ca-125 will result in a longer time until the next or different treatment for the patient's cancer. the study will also evaluate how delaying the start of maintenance therapy will affect symptoms; physical functioning; quality of life; and impact on finances.

this is a phase ii trial will investigate if waiting until the time of chemical recurrence, denoted by rising ca125, to start a parp inhibitor will lead to an improved time to next therapy with improved quality of life and at a lower financial toxicity. parp-i have shown efficacy as both monotherapy and as maintenance therapy. this trial will explore whether patients with recurrent ovarian cancer could derive the same efficacy benefit from a delayed start of a parp-i compared to immediate maintenance therapy. delayed start would have the benefit of sparing the physical, psychological, and financial toxicity associated with prolonged treatment. this approach would be particularly relevant in a population of platinum-sensitive patients who can have prolonged treatment-free intervals. with widespread use of parp-i, regardless of timing, understanding, and overcoming parp-i resistance is becoming a major clinical need. enrollment will start within 8 weeks of completion of platinum-based treatment. monitored with ca 125 levels every 28 days. olaparib will be started when ca 125 rises by two-fold of their nadir value. olaparib will be dosed at 300 mg orally twice a day, 28 days of treatment will be a cycle. follow-up will consist of ca125 drawn every 28 days and ct scans obtained at doubling of ca- 125 and then every 12 weeks\* to assess for recurrence or progression. clinician- and patient-reported adverse events recorded every 28 days. cancer-related worry and distress assessed every 28 days. measures of quality of life and physical function, and financial toxicity assessed every 12 weeks.

Eligibility criteria:
inclusion criteria: * patient has platinum-sensitive, recurrent ovarian, fallopian-tube or peritoneal cancer. platinum sensitivity is defined as complete clinical remission after frontline chemotherapy lasting greater than 6 months * patient has completed at least 2 courses of platinum-based chemotherapy with a pr or cr as defined by the response evaluation criteria in solid tumors (recist) v1.139 or a ca-125 response, according to gynecological cancer intergroup (gcig) criteria40 * brca testing required (results not needed for registration) * ecog performance status score of 0, 1, or 2 (see appendix a) * life expectancy greater than 6 months * normal organ and marrow function as defined: absolute neutrophil count (anc) ≥ 1.5 x 109/l; platelets ≥ 100 x 109/l; hemoglobin (hgb) ≥ 8 g/dl (blood transfusions to reach this amount are allowed); serum creatinine ≤ 1.5 mg/dl; total serum bilirubin ≤ 1.5 x uln; ast and alt ≤ 2.5 x uln * able to take oral medication * not pregnant and not breastfeeding * able to understand and willingness to sign a written informed consent document * patients must be enrolled within 8 weeks of completing last cycle of chemotherapy exclusion criteria: * patient has had a prior invasive malignancy diagnosed within the last five years (except \[1\] non-melanoma skin cancer or \[2\] prior in situ carcinoma of the cervix or breast \[3\] has been without evidence of invasive disease for greater than 3 years) * patients receiving any other investigational agents * history of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib * uncontrolled intercurrent illness that could affect their participation in the study including, but not limited to, ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; known inadequately controlled hypertension; significant pulmonary disease including dyspnea at rest, patients requiring supplemental oxygen, or poor pulmonary reserve; or psychiatric illness/social situations that would limit compliance with study requirements * impairment of gastrointestinal function or disease that may significantly alter the absorption of olaparib * patients who have received prior treatment with a parp inhibitor * history of noncompliance to medical regimens

Keywords: parp-i brca mutation epithelial ovarian cancer (eoc) olaparib platinum sensitive recurrent ovarian carcinoma poly adp-ribose polymerase (parp) inhibitor.