To Evaluate the Safety and Efficacy of Ipatasertib (GDC-0068) in Combination With Paclitaxel in Platinum-resistant Recurrent Epithelial Ovarian Cancer

Inclusion Criteria:

* Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses

  o If a patient declines to participate in any voluntary exploratory research and/or genetic component of the study, there will be no penalty or loss of benefit to the patient and he/she will not be excluded from other aspects of the study
* Aged at least 18 years at time of signing informed consent
* A pathologic (histology or cytology) confirmed diagnosis of epithelial ovarian cancer, including fallopian or primary peritoneal cancer

  o low grade serous histology is excluded
* Radiographic evidence of recurrent epithelial ovarian cancer (ovarian, fallopian tube, or primary peritoneal cancer) that has become "platinum-resistant," defined as progression of disease within 6 months from the last dose of platinum-based chemotherapy, or platinum refractory
* Not a candidate for cytoreductive surgery
* Measurable disease (at least one lesion that can be accurately assessed repeatedly by CT or MRI) as evidenced on pre-treatment baseline CT of Chest/Abdomen/Pelvis, MRI, or PET/CT, or evaluable disease (defined as anything non-measurable- pleural effusions, lesions \<1cm, etc).
* World Health Organization (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
* Up to 3 lines of prior cytotoxic chemotherapy
* Previously received bevacizumab
* Has not received weekly paclitaxel-containing regimen, EXCEPT for in the front-line setting

  o Patients with prior paclitaxel reactions may be enrolled if they have been successfully re-treated with steroid pre-medication in the past
* Patients must use adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing (within 7 days) if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:

  * Post-menopausal defined as aged more than 50 years and amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments
  * Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 28 days after the last dose of study treatment. Women must refrain from donating eggs during this same period.

Exclusion Criteria:

* Treatment with any of the following:

  * Any investigational agents or study drugs from a previous clinical study within 28 days of the first dose of study treatment
  * Any other chemotherapy, immunotherapy or anticancer agents within 14 days of the first dose of study treatment
  * Potent inhibitors or inducers or substrates of CYP3A4 or substrates of CYP2D6 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort)
  * Any prior exposure to Ipatasertib
* Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment
* Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment
* With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment
* Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 2 weeks prior to start of study treatment
* Concurrent use of endocrine therapy
* As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
* Any of the following cardiac criteria:

  * Any clinically important abnormalities in rhythm, known prolonged QTc, conduction or morphology of resting ECG, complete left bundle branch block, third degree heart block
  * Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure NYHA Grade 2 or greater
  * Uncontrolled hypotension - Systolic BP \<90mmHg and/or diastolic BP \<50mmHg
  * Left ventricular ejection fraction (LVEF) below lower limit of normal for site
* Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:

  * Absolute neutrophil count \< 1.5 x 109/L
  * Platelet count \< 100 x 109/L
  * Hemoglobin \< 9 g/L
  * Alanine aminotransferase \> 2.5 times the upper limit of normal (ULN)
  * Aspartate aminotransferase \> 2.5 times ULN
  * Total bilirubin \> 1.5 times ULN
  * Creatinine \>1.5 times ULN concurrent with creatinine clearance \< 50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is \> 1.5 times ULN
  * Proteinuria 3+ on dipstick analysis or \>500mg/24 hours
  * Sodium or potassium outside normal reference range for site
* Peripheral neuropathy grade 2 or greater
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption Ipatasertib
* History of hypersensitivity to Ipatasertib, or drugs with a similar chemical structure or class to Ipatasertib
* Clinically significant abnormalities of glucose metabolism as defined by any of the following:

  * Diagnosis of type I or type II diabetes mellitus requiring insulin
  * A baseline fasting glucose value of ≥ 200 mg/dL (fasting glucose value to be obtained only if non-fasting glucose \>200mg/dL)
  * Glycosylated hemoglobin (HbA1C) \>7.5%
* Uncontrolled pleural effusion, pericardial effusion, or ascites
* Other malignancies within the past 3 years, with the exception of adequately resected basal or squamous carcinoma of the skin
* Clinically significant pulmonary symptoms or disease
* Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements