Phase Ib Study of Olaparib Plus Weekly Carboplatin and Paclitaxel in Relapsed Ovarian Cancer

Inclusion Criteria:

Advanced (stage III or IV), histologically or cytologically documented ovarian cancer or serious uterine cancer patients who relapsed after primary therapy with a platinum and a taxane. This includes:

Platinum sensitive: relapsed at least 6 months following platinum treatment
Platinum refractory: the cancer grew while on platinum treatment
Platinum resistant: recurrence within 6 months of platinum treatment
Must have failed first line treatment
ECOG performance status 0-2
Must be able to swallow and retain oral medication
Life expectancy greater than 16 weeks

Must have normal organ and bone marrow function defined as follows:

Hemoglobin ≥ 9.0 g/dL
Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
White blood cells (WBC) > 3 x 10^9/L
Platelet count ≥ 100 10^9/L
Total bilirubin ≤ 1.5 x institutional upper limit of normal
AST (SGOT)/ALT (SGPT) ≤ x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5 ULN
Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)

Exclusion Criteria:

Any previous treatment with a PARP inhibitor, including olaparib
Any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment (or longer period depending on the defined characteristics of the agents used)
Currently receiving the following classes of inhibitors of CYP3A4: azole antifungals, macrolide antibiotics, and protease inhibitors
Second primary cancer except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
Symptomatic uncontrolled brain metastases
Major surgery within 2 weeks of starting study treatment
Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)
Known active hepatic disease (i.e. Hepatitis B or C)
Uncontrolled seizures
History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin or paclitaxel