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