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Trial of Nab-Sirolimus in Combination With Letrozole in Patients With Advanced or Recurrent Endometrioid Endometrial Cancer

Primary Purpose

Endometrial Cancer, Endometrioid Tumor, Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
nab-sirolimus
Sponsored by
Aadi Bioscience, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Endometrial Cancer focused on measuring nab-Sirolimus, FYARRO, Letrozole, Endometrial, Recurrent, ABI-009, Endometrial Carcinoma, Endometrioid Tumor, Endometrial Cancer, Recurrent Endometrial Carcinoma, Endometrioid Endometrial Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients must have clinically confirmed advanced or recurrent endometrioid endometrial carcinoma. Histologic documentation of the recurrence is suggested but not required. All patients must have 1 or more measurable target lesion at baseline by computed tomography (CT; or magnetic resonance imaging [MRI] if CT scans are contraindicated) as defined by RECIST version 1.1. Patients must have EEC that is metastatic or locally advanced where surgical resection is not an option or likely to result in severe morbidity. Prior treatment history: Adjuvant setting - treatment with chemotherapy, hormonal therapy,checkpoint inhibitors, and/or other therapy is permitted as long as theadjuvant therapy ended ≥6 months from enrollment. Recurrent/advanced/metastatic setting - treatment with 0-1 prior chemotherapy regimens is permitted (patients may be naïve to chemotherapy); chemotherapy must have been completed ≥3 months prior to enrollment. Patients are permitted to have received adjuvant chemotherapy and no more than 1 line of chemotherapy in the recurrent/advanced/metastatic setting. Non-chemotherapy-based treatment (eg, checkpoint inhibitors, hormonal therapy, and/or small molecule agents) is permitted at any point as long as therapy ended ≥4 weeks prior to enrollment. Patients who have received prior therapy in the recurrent/advanced/metastatic setting must have achieved a complete or partial response(investigator-assessed) to at least 1 therapy. Age: 18 years or older. Patient must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate liver function: Total bilirubin ≤1.5 × upper limit of normal (ULN) (unless due to Gilbert's syndrome, then ≤3 × ULN) Aspartate aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if attributable to liver metastases) Adequate renal function: creatinine clearance (CrCL) ≥30 mL/min based on Cockcroft-Gault Adequate hematologic parameters: Absolute neutrophil count (ANC) ≥1.0 × 109/L (growth factor support allowed) Platelet count ≥100,000/mm3 (100 × 109/L) (transfusion and/or growth factor support allowed) Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed) Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be less than or equal to 350 mg/dL. Minimum of 4 weeks since any major surgery, completion of radiation, or completion of prior systemic anticancer therapy, or at least 5 half-lives if the prior therapy is a single agent small-molecule therapeutic, and adequately recovered from the acute toxicities of any prior therapy, including neuropathy, to Grade ≤1. Non-pregnant and non-breastfeeding female: Females of childbearing potential must agree to use effective contraception or abstinence without interruption from 28 days prior to starting nab-Sirolimus through 3 months after the last dose of nab-Sirolimus and have a negative serum pregnancy test (beta human chorionic gonadotropin [β-hCG]) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. A second form of birth control is required even if she has had a tubal ligation. Sexual abstinence is considered a highly effective contraceptive method only if defined as refraining from heterosexual intercourse from 28 days prior to starting study medication throughout 3 months after last dose of study medication. The reliability of sexual abstinence should be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the patient. The patient understands and signs the informed consent. Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures. Patients with a known history of human immunodeficiency virus (HIV)infection are eligible if: There has been no acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection in 12 months prior to enrollment. The patient has been receiving an antiretroviral therapy regimen for≥4 weeks and the HIV viral load is <400 copies/mL prior to enrollment. Antiretroviral therapy regimen does not include strong cytochrome(CYP)3A4 inhibitors or inducers Exclusion Criteria: Prior treatment with an mTOR inhibitor, including nab-sirolimus. Patients with known inactivating TSC1 or TSC2 alterations (based on tissue or liquid next generation sequencing [NGS]) unless the PRECISION 1 study (NCT05103358) has been closed to enrollment. Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective treatment, either ongoing or completed ≤7 days prior to enrollment. Patients with primary refractory disease (ie, those who have never achieved a complete or partial response to prior therapy) are not permitted on study. Patients with the following are excluded: Known or suspected brain metastases. Severe heart disease defined as unstable angina pectoris, New York Heart Association (NYHA) Class III or IV congestive heart failure, myocardial infarction ≤6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease. Severe lung disease defined as a diffusing capacity for carbon monoxide (DLCO) that is ≤50% of normal predicted value and/or an O2 saturation ≤88% at rest on room air (Note: spirometry and pulmonary function tests [PFTs] are not required to be performed unless clinically indicated). Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy. A history of malignancies other than the one under treatment unless the patient is disease-free for more than 5 years from completion of therapy administered with curative intent. Controlled non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer, certain low grade hematologic malignancies (eg, chronic lymphocytic leukemia [CLL], follicular lymphoma, etc), or other adequately treated carcinoma in situ may be eligible, after discussion with the Medical Monitor. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension. Active hepatitis B and/or hepatitis C infection and detectable viral load despite antiviral therapy Required use of concomitant medications with strong CYP3A4 interactions (induction or inhibition) should be discontinued (strong inhibitors include ketoconazole, itraconazole, voriconazole, erythromycin, clarithromycin, telithromycin; strong inducers include rifampin and rifabutin). These agents must be discontinued prior to first dose of nab-sirolimus.

Sites / Locations

  • University Oklahoma Stephenson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Endometrioid Endometrial Cancer

Arm Description

Patients with advanced or recurrent endometrioid endometrial carcinoma

Outcomes

Primary Outcome Measures

Overall response rate (ORR)
ORR, defined as the proportion of patients with best overall response (BOR) of confirmed partial response (PR) or complete response (CR) from the time of study treatment initiation until progression of disease (PD) as determined by the Investigator using RECIST v1.1.

Secondary Outcome Measures

Duration of response (DOR)
Determined for patients with BOR of confirmed CR or PR
Disease Control Rate (DCR): CR or PR
BOR of confirmed CR or PR (either of any duration) or stable disease (SD) following study treatment initiation (by IRR)
Time to response (TTR)
Time from study treatment initiation to initial measurement of CR or PR, where CR or PR is subsequently confirmed
Progression-free survival (PFS)
Number of months from study treatment initiation to the date of disease progression 3 or death due to any cause
Overall survival (OS)
Number of months from study treatment initiation to the date of death due to any cause or last follow up date if alive
Incidence and severity
Of treatment-emergent and treatment-related adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

Full Information

First Posted
August 10, 2023
Last Updated
August 16, 2023
Sponsor
Aadi Bioscience, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05997017
Brief Title
Trial of Nab-Sirolimus in Combination With Letrozole in Patients With Advanced or Recurrent Endometrioid Endometrial Cancer
Official Title
A Phase 2 Multi-center Open-label Trial of Nab-Sirolimus in Combination With Letrozole in Advanced or Recurrent Endometrioid Endometrial Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 2023 (Anticipated)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
October 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aadi Bioscience, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A Phase 2 Multi-center Open-label Trial of nab-Sirolimus in Combination with Letrozole in Advanced or Recurrent Endometrioid Endometrial Cancer
Detailed Description
This is a prospective phase 2, open-label, multi-institutional study to evaluate the efficacy and safety of nab-sirolimus + letrozole in patients with advanced or recurrent endometrioid endometrial carcinoma who have received 0-1 prior lines of chemotherapy in the recurrent/metastatic setting. Patients will be treated with nab-sirolimus (given IV on Days 1 and 8 in a 21-day cycle, combined with letrozole (orally, daily) until unacceptable toxicity or disease progression, or until in the opinion of the Investigator the patient is no longer benefiting from therapy, or at patient discretion.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometrial Cancer, Endometrioid Tumor, Cancer, Tumor, Recurrent Endometrial Carcinoma, Endometrioid Endometrial Cancer
Keywords
nab-Sirolimus, FYARRO, Letrozole, Endometrial, Recurrent, ABI-009, Endometrial Carcinoma, Endometrioid Tumor, Endometrial Cancer, Recurrent Endometrial Carcinoma, Endometrioid Endometrial Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Endometrioid Endometrial Cancer
Arm Type
Experimental
Arm Description
Patients with advanced or recurrent endometrioid endometrial carcinoma
Intervention Type
Drug
Intervention Name(s)
nab-sirolimus
Other Intervention Name(s)
ABI-009
Intervention Description
Prospective Phase 2, open-label, multi-institutional study to evaluate the efficacy and safety of nab-sirolimus + letrozole in patients
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
ORR, defined as the proportion of patients with best overall response (BOR) of confirmed partial response (PR) or complete response (CR) from the time of study treatment initiation until progression of disease (PD) as determined by the Investigator using RECIST v1.1.
Time Frame
12 Months
Secondary Outcome Measure Information:
Title
Duration of response (DOR)
Description
Determined for patients with BOR of confirmed CR or PR
Time Frame
12 Months
Title
Disease Control Rate (DCR): CR or PR
Description
BOR of confirmed CR or PR (either of any duration) or stable disease (SD) following study treatment initiation (by IRR)
Time Frame
12 Months
Title
Time to response (TTR)
Description
Time from study treatment initiation to initial measurement of CR or PR, where CR or PR is subsequently confirmed
Time Frame
12 Months
Title
Progression-free survival (PFS)
Description
Number of months from study treatment initiation to the date of disease progression 3 or death due to any cause
Time Frame
12 Months
Title
Overall survival (OS)
Description
Number of months from study treatment initiation to the date of death due to any cause or last follow up date if alive
Time Frame
24 Months
Title
Incidence and severity
Description
Of treatment-emergent and treatment-related adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Time Frame
12 Months

10. Eligibility

Sex
All
Gender Based
Yes
Gender Eligibility Description
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have clinically confirmed advanced or recurrent endometrioid endometrial carcinoma. Histologic documentation of the recurrence is suggested but not required. All patients must have 1 or more measurable target lesion at baseline by computed tomography (CT; or magnetic resonance imaging [MRI] if CT scans are contraindicated) as defined by RECIST version 1.1. Patients must have EEC that is metastatic or locally advanced where surgical resection is not an option or likely to result in severe morbidity. Prior treatment history: Adjuvant setting - treatment with chemotherapy, hormonal therapy,checkpoint inhibitors, and/or other therapy is permitted as long as theadjuvant therapy ended ≥6 months from enrollment. Recurrent/advanced/metastatic setting - treatment with 0-1 prior chemotherapy regimens is permitted (patients may be naïve to chemotherapy); chemotherapy must have been completed ≥3 months prior to enrollment. Patients are permitted to have received adjuvant chemotherapy and no more than 1 line of chemotherapy in the recurrent/advanced/metastatic setting. Non-chemotherapy-based treatment (eg, checkpoint inhibitors, hormonal therapy, and/or small molecule agents) is permitted at any point as long as therapy ended ≥4 weeks prior to enrollment. Patients who have received prior therapy in the recurrent/advanced/metastatic setting must have achieved a complete or partial response(investigator-assessed) to at least 1 therapy. Age: 18 years or older. Patient must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate liver function: Total bilirubin ≤1.5 × upper limit of normal (ULN) (unless due to Gilbert's syndrome, then ≤3 × ULN) Aspartate aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if attributable to liver metastases) Adequate renal function: creatinine clearance (CrCL) ≥30 mL/min based on Cockcroft-Gault Adequate hematologic parameters: Absolute neutrophil count (ANC) ≥1.0 × 109/L (growth factor support allowed) Platelet count ≥100,000/mm3 (100 × 109/L) (transfusion and/or growth factor support allowed) Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed) Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be less than or equal to 350 mg/dL. Minimum of 4 weeks since any major surgery, completion of radiation, or completion of prior systemic anticancer therapy, or at least 5 half-lives if the prior therapy is a single agent small-molecule therapeutic, and adequately recovered from the acute toxicities of any prior therapy, including neuropathy, to Grade ≤1. Non-pregnant and non-breastfeeding female: Females of childbearing potential must agree to use effective contraception or abstinence without interruption from 28 days prior to starting nab-Sirolimus through 3 months after the last dose of nab-Sirolimus and have a negative serum pregnancy test (beta human chorionic gonadotropin [β-hCG]) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. A second form of birth control is required even if she has had a tubal ligation. Sexual abstinence is considered a highly effective contraceptive method only if defined as refraining from heterosexual intercourse from 28 days prior to starting study medication throughout 3 months after last dose of study medication. The reliability of sexual abstinence should be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the patient. The patient understands and signs the informed consent. Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures. Patients with a known history of human immunodeficiency virus (HIV)infection are eligible if: There has been no acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection in 12 months prior to enrollment. The patient has been receiving an antiretroviral therapy regimen for≥4 weeks and the HIV viral load is <400 copies/mL prior to enrollment. Antiretroviral therapy regimen does not include strong cytochrome(CYP)3A4 inhibitors or inducers Exclusion Criteria: Prior treatment with an mTOR inhibitor, including nab-sirolimus. Patients with known inactivating TSC1 or TSC2 alterations (based on tissue or liquid next generation sequencing [NGS]) unless the PRECISION 1 study (NCT05103358) has been closed to enrollment. Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective treatment, either ongoing or completed ≤7 days prior to enrollment. Patients with primary refractory disease (ie, those who have never achieved a complete or partial response to prior therapy) are not permitted on study. Patients with the following are excluded: Known or suspected brain metastases. Severe heart disease defined as unstable angina pectoris, New York Heart Association (NYHA) Class III or IV congestive heart failure, myocardial infarction ≤6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease. Severe lung disease defined as a diffusing capacity for carbon monoxide (DLCO) that is ≤50% of normal predicted value and/or an O2 saturation ≤88% at rest on room air (Note: spirometry and pulmonary function tests [PFTs] are not required to be performed unless clinically indicated). Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy. A history of malignancies other than the one under treatment unless the patient is disease-free for more than 5 years from completion of therapy administered with curative intent. Controlled non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer, certain low grade hematologic malignancies (eg, chronic lymphocytic leukemia [CLL], follicular lymphoma, etc), or other adequately treated carcinoma in situ may be eligible, after discussion with the Medical Monitor. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension. Active hepatitis B and/or hepatitis C infection and detectable viral load despite antiviral therapy Required use of concomitant medications with strong CYP3A4 interactions (induction or inhibition) should be discontinued (strong inhibitors include ketoconazole, itraconazole, voriconazole, erythromycin, clarithromycin, telithromycin; strong inducers include rifampin and rifabutin). These agents must be discontinued prior to first dose of nab-sirolimus.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aadi Bioscience Medical Information
Phone
1-888-246-2234
Email
MedInfo@aadibio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Willis Navarro, MD
Organizational Affiliation
Aadi Bioscience
Official's Role
Study Director
Facility Information:
Facility Name
University Oklahoma Stephenson Cancer Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lauren Dockery, MD

12. IPD Sharing Statement

Learn more about this trial

Trial of Nab-Sirolimus in Combination With Letrozole in Patients With Advanced or Recurrent Endometrioid Endometrial Cancer

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