Nab-Sirolimus and Endocrine Therapy in Recurrent Low Grade Serous Ovarian Cancer (NARETO)

Inclusion Criteria:

1. Patients must have a histologic confirmed low-grade serous ovarian cancer withclinical evidence of reoccurrence.

2. All patients must have measurable disease as defined by RECIST version 1.1.

3. ECOG Performance status must be 0-1.

4. Adequate bone marrow, hepatic and renal function as defined by the protocol.

5. At least 4 weeks must have elapsed since the patient underwent any major surgery.

6. At least 2 weeks must have elapsed since the patient received any radiation therapy.

7. Patients must have signed an IRN approved informed consent and authorizationpermitting release of personal health information.

8. All patients must be at least 18 years of age.

9. Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe investigational regimen are eligible for this trial.

10. Patients of childbearing potential must have a negative serum pregnancy test priorto the study entry and be practicing a highly effective form of contraception.During the study treatment and for 12 weeks after stopping nab-sirolimus and 12months after stopping Fulvestrant. Highly effective contraceptive methods includecombination of any two of the following as defined in the protocol.

Exclusion Criteria:

1. Patients who have previously received nab-sirolimus, any other mTOR inhibitor or anyagent targeting the PI3K/AKT/mTOR pathway. (Prior MEKi is not exclusionary; up toone prior cytotoxic therapy is permissible.)

2. Known intolerance or hypersensitivity to nab-sirolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus).

3. Patients receiving chronic treatment with systemic steroids or anotherimmunosuppressive agent if >10 mg prednisone equivalent per day

4. Patients with active or uncontrolled systemic infection requiring IV antibiotics,either ongoing or completed ≤7 days prior to enrollment.

5. Known severely impaired lung function, including:

• CTCAE grade 2 (or greater) hypoxia (decreased oxygen saturation with exercise [e.g., pulse oximeter <88%]; intermittent supplemental oxygen)

6. Patients with known history or current symptoms of cardiac disease, or history oftreatment with cardiotoxic agents, should have a clinical risk assessment of cardiacfunction using the New York Heart Association Functional Classification 1. To beeligible for this trial, patients should be class 2B or better.

7. Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6months prior to the first date of study therapy.

8. Patients who are hypersensitive to albumin.

9. Patients who are pregnant or breast-feeding.

10. Patients with brain metastases. Patients recently treated for brain metastases areeligible as long as they have been off steroids or RT for at least 2 weeks.

11. Known HIV-infected patients requiring anti-retroviral therapy that are strong CYP3A4inhibitors or inducers.

12. Patients with active bleeding or pathologic conditions that carry high risk ofbleeding, such as known bleeding disorder or coagulopathy.

13. Patients who are currently part of or have participated in any clinicalinvestigation with an investigational drug within 28 days prior to dosing or 5half-lives whichever is shorter.

14. Active Hepatitis B or Hepatitis C, with detectable viral load.

• For patients with evidence of chronic hepatitis B virus (HBV) infection, theHBV viral load must be undetectable on suppressive therapy, if indicated.Patients with a history of hepatitis C virus (HCV) infection must have beentreated and cured. For patients with HCV infection who are currently ontreatment, they are eligible if they have an undetectable HCV viral load.

15. Uncontrolled hypertension (systolic blood pressure ≥160 mm-Hg and/or diastolic bloodpressure ≥100 mm Hg).

16. Patients who are unable to discontinue concomitant medication with CYP3A4 stronginducers (eg, rifampin, rifabutin), and known CYP3A4 substrates with a narrowtherapeutic window (eg, fentanyl, alfentanil, astemizole, cisapride,dihydroergotamine, pimozide, quinidine, or terfenadine) at least 5 half-lives priorto receiving the first dose of nab-sirolimus. Medical Monitor approval required ifpatient is taking any of the medications listed above.