Trial Title:
Trial of Nab-Sirolimus in Combination With Letrozole in Patients With Advanced or Recurrent Endometrioid Endometrial Cancer
NCT ID:
NCT05997017
Condition:
Endometrial Cancer
Endometrioid Tumor
Cancer
Tumor
Recurrent Endometrial Carcinoma
Endometrioid Endometrial Cancer
Conditions: Official terms:
Carcinoma
Endometrial Neoplasms
Recurrence
Sirolimus
Conditions: Keywords:
nab-Sirolimus
FYARRO
Letrozole
Endometrial
Recurrent
ABI-009
Endometrial Carcinoma
Endometrioid Tumor
Endometrial Cancer
Recurrent Endometrial Carcinoma
Endometrioid Endometrial Cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
nab-sirolimus
Description:
Prospective Phase 2, open-label, multi-institutional study to evaluate the efficacy and
safety of nab-sirolimus + letrozole in patients
Arm group label:
Endometrioid Endometrial Cancer
Other name:
ABI-009
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients must have clinically confirmed advanced or recurrent endometrioid
endometrial carcinoma. Histologic documentation of the recurrence is suggested but
not required.
2. 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.
3. Patients must have EEC that is metastatic or locally advanced where surgical
resection is not an option or likely to result in severe morbidity.
4. Prior treatment history:
1. 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.
2. 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.
3. 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.
4. 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.
5. Age: 18 years or older.
6. Patient must have Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1.
7. Adequate liver function:
1. Total bilirubin ≤1.5 × upper limit of normal (ULN) (unless due to Gilbert's
syndrome, then ≤3 × ULN)
2. Aspartate aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if attributable to liver
metastases)
8. Adequate renal function: creatinine clearance (CrCL) ≥30 mL/min based on
Cockcroft-Gault
9. Adequate hematologic parameters:
1. Absolute neutrophil count (ANC) ≥1.0 × 109/L (growth factor support allowed)
2. Platelet count ≥100,000/mm3 (100 × 109/L) (transfusion and/or growth factor
support allowed)
3. Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed)
10. Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be
less than or equal to 350 mg/dL.
11. 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.
12. Non-pregnant and non-breastfeeding female:
1. 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.
2. 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.
13. The patient understands and signs the informed consent.
14. Willingness and ability to comply with scheduled visits, laboratory tests, and other
study procedures.
15. Patients with a known history of human immunodeficiency virus (HIV)infection are
eligible if:
1. There has been no acquired immunodeficiency syndrome (AIDS)-defining
opportunistic infection in 12 months prior to enrollment.
2. The patient has been receiving an antiretroviral therapy regimen for≥4 weeks
and the HIV viral load is <400 copies/mL prior to enrollment.
3. Antiretroviral therapy regimen does not include strong cytochrome(CYP)3A4
inhibitors or inducers
Exclusion Criteria:
1. Prior treatment with an mTOR inhibitor, including nab-sirolimus.
2. 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.
3. Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective
treatment, either ongoing or completed ≤7 days prior to enrollment.
4. Patients with primary refractory disease (ie, those who have never achieved a
complete or partial response to prior therapy) are not permitted on study.
5. Patients with the following are excluded:
1. Known or suspected brain metastases.
2. 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.
3. 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).
4. Nonmalignant medical illnesses that are uncontrolled or whose control may be
jeopardized by the treatment with the study therapy.
5. 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.
6. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic
blood pressure ≥100 mmHg
7. Patients with history of interstitial lung disease and/or pneumonitis, or
pulmonary hypertension.
8. Active hepatitis B and/or hepatitis C infection and detectable viral load
despite antiviral therapy
6. 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.
Gender:
All
Gender based:
Yes
Gender description:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Michael Birrer, MD, PhD
Address:
City:
Little Rock
Zip:
72205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Aaron Holley
Email:
jaholley@uams.edu
Contact backup:
Last name:
Matthew Kovak
Email:
mrkovak@uams.edu
Facility:
Name:
Mount Sinai Comprehensive Cancer Center
Address:
City:
Miami Beach
Zip:
33140
Country:
United States
Status:
Recruiting
Contact:
Last name:
Michelle McClosky
Phone:
305-674-2625
Email:
Michelle.Mcclosky@msmc.com
Investigator:
Last name:
Brian Slomovitz, MD
Email:
Principal Investigator
Facility:
Name:
Women's Cancer Center of Nevada
Address:
City:
Las Vegas
Zip:
89106
Country:
United States
Status:
Recruiting
Contact:
Last name:
Thania Escamilla
Phone:
702-693-6870
Email:
tescamilla@wccenter.com
Contact backup:
Last name:
Jacky Amador
Phone:
702-693-6870
Email:
jamador@wccenter.com
Investigator:
Last name:
Nicola M Spirtos, MD
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Angela Green, MD
Phone:
646-888-4224
Email:
greena@mskcc.org
Investigator:
Last name:
Angela Green, MD
Email:
Principal Investigator
Facility:
Name:
Levine Cancer Institute
Address:
City:
Charlotte
Zip:
28204
Country:
United States
Status:
Recruiting
Contact:
Last name:
Leah J Wilson, BS, RN, OCN
Phone:
980-442-2333
Email:
leah.j.wilson@atriumhealth.org
Investigator:
Last name:
Allison M Puechi, MD
Email:
Principal Investigator
Facility:
Name:
Oklahoma University Stephenson Cancer Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christine Pappaterra
Phone:
405-271-8777
Email:
Christine-pappaterra@ouhsc.edu
Investigator:
Last name:
Lauren Dockery, MD
Email:
Principal Investigator
Facility:
Name:
Women & Infants Hospital
Address:
City:
Providence
Zip:
02905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Pamela Smith
Phone:
401-274-1122
Phone ext:
48181
Email:
oncologyresearch@wihri.org
Investigator:
Last name:
Cara Mathews, MD
Email:
Principal Investigator
Facility:
Name:
Texas Oncology - Tyler
Address:
City:
Tyler
Zip:
75702
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shelly Maxfield, CCRP
Phone:
903-579-9840
Email:
shelly.maxfield@usoncology.com
Investigator:
Last name:
Anna Priebe, MD
Email:
Principal Investigator
Facility:
Name:
Swedish Cancer Institute
Address:
City:
Seattle
Zip:
98104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Anh Lam
Phone:
206-386-2227
Email:
Anh.lam@swedish.org
Investigator:
Last name:
Fernanda Musa, MD
Email:
Principal Investigator
Start date:
December 28, 2023
Completion date:
October 2026
Lead sponsor:
Agency:
Aadi Bioscience, Inc.
Agency class:
Industry
Source:
Aadi Bioscience, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05997017
