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

Phase 2

Not yet recruiting

• Conditions: Low Grade Ovarian Serous Adenocarcinoma
• Interventions: Drug: nab-Sirolimus; Drug: Fulvestrant

• Registration Number: NCT06494150
• Lead Sponsor: University of Oklahoma

Brief Summary

This single arm phase II study proposes to evaluate the efficacy and safety of nab-sirolimus + endocrine therapy (Fulvestrant) in patients with recurrent low grade serous ovarian cancer (LGSOC).

Detailed Description

Patients with histologic confirmed Low Grade Serous Ovarian Cancer with measurable disease should have a pre-dose tumor biopsy.
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Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2024-07-02
• Study First Submitted QC: 2024-07-02
• Study First Posted: 2024-07-10
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-11
• Last Update Posted: 2024-11-13
• Study Start: 2024-12
• Primary Completion: 2027-08
• Study Completion: 2029-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 37

Inclusion Criteria

1. Patients must have a histologic confirmed low-grade serous ovarian cancer with clinical 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 authorization permitting 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 treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
10. Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing a highly effective form of contraception. During the study treatment and for 6 months after stopping the treatment. Highly effective contraceptive methods include combination of any two of the following:

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Exclusion Criteria

1. Patients who have previously received nab-sirolimus, any other mTOR inhibitor or any agent targeting the PI3K/AKT/mTOR pathway. (Prior MEKi is not exclusionary; up to one 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 another immunosuppressive 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 of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification 1. To be eligible for this trial, patients should be class 2B or better.

7. Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6 months 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 are eligible 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 CYP3A4 inhibitors or inducers.

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

13. Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 28 days prior to dosing or 5 half-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, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

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

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
nab-sirolimus + Fulvestrant	nab-Sirolimus	Patients will be treated with the combination nab-sirolimus (100 mg/m2 intravenous injection on day 1 and 8 of each 21-day cycle) and fulvestrant (500mg intramuscular injection on days 1 and 15 of cycle 1 and then every 21 days).
nab-sirolimus + Fulvestrant	Fulvestrant	Patients will be treated with the combination nab-sirolimus (100 mg/m2 intravenous injection on day 1 and 8 of each 21-day cycle) and fulvestrant (500mg intramuscular injection on days 1 and 15 of cycle 1 and then every 21 days).

Primary Outcome Measures

Name	Time	Method
Incidence of patients with ≥ grade 3 adverse events.	3 years	Review of adverse events that have occurred to determine the toxicity for the proposed treatment regimen.
The percentage of people in a treatment group who have a partial or complete response to the treatment within a certain period of time as measured by RECIST version 1.1.	3 years	The primary analysis is preplanned to occur when the last patient enrolled has been treated for 6 months.

Secondary Outcome Measures

Name	Time	Method
Duration of response from a subjects first scan to disease progression or death.	Up to 3 years	Determine the length of time from the date subjects have partial or complete response to treatment until the date the subjects have disease progression.
Proportion of patients who have remained progression-free for 6-months.	3 years	Proportion of patients on the proposed treatment combination who have not had any disease progression for at least 6 months.

Trial Locations

Locations (1)

OU Health Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States