Delayed Initiation of Olaparib Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer

Phase IIA Trial of Delayed Initiation of Olaparib Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer

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.

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