Trial Title:
Trial of Nab-sirolimus in Patients With Well-differentiated Neuroendocrine Tumors (NETs) of the Gastrointestinal Tract, Lung, or Pancreas Who Have Not Received Prior Treatment With mTOR Inhibitors
NCT ID:
NCT05997056
Condition:
Neuroendocrine Tumors
NET
Pancreatic Neuroendocrine Tumor
Gastrointestinal Neuroendocrine Tumor
Pulmonary Neuroendocrine Tumor
Conditions: Official terms:
Neoplasms
Neuroendocrine Tumors
Adenoma, Islet Cell
Intestinal Neoplasms
Pancreatic Neoplasms
Stomach Neoplasms
Sirolimus
Conditions: Keywords:
FYARRO
nab-sirolimus
ABI-009
Neuroendocrine Tumors
NET
Pancreatic Neuroendocrine Tumor
Gastrointestinal Neuroendocrine Tumor
Pulmonary Neuroendocrine Tumor
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 single arm, open-label, multi-institutional study to determine the
efficacy and safety prospective of nab-sirolimus administered by IV infusion
Arm group label:
neuroendocrine tumors
Other name:
ABI-009
Summary:
A Phase 2 multi-center, open-label, single arm study of nab-sirolimus in patients with
well-differentiated neuroendocrine tumors (NETs) of the gastrointestinal tract, lung, or
pancreas who have not received prior treatment with mTOR inhibitors
Detailed description:
This is a prospective phase 2 single arm, open-label, multi-institutional study to
determine the efficacy and safety prospective of nab-sirolimus and patients with
functional or non-functional, well-differentiated, locally advanced unresectable in
metastatic NETs of the GI tract, lung, or pancreas.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients with functional or non-functional, well-differentiated, locally advanced
unresectable or metastatic NETs of the GI tract, lung, or pancreas who have received
2 or less prior lines of therapy excluding somatostatin analogs
2. Patients with functional NETs may enroll if:
1. the patient has been on a stable dose of an somatostatin analogs for ≥12 weeks
and
2. the patient has experienced disease progression while on stable somatostatin
analogs dose
3. Patients must have 1 or more measurable target lesions by RECIST v1.1
4. Age: 18 years or older
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or Karnofsky
Performance Status (KPS) ≥80
6. Adequate liver function:
1. Total bilirubin ≤1.5 × upper limit of normal (ULN) (unless due to Gilbert's
syndrome or attributable to liver metastases, then ≤3 × ULN)
2. Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤2.5 × ULN (≤5
× ULN if attributable to liver metastases)
7. Adequate renal function: creatinine clearance ≥30 mL/min, Cockcroft-Gault creatinine
clearance = ((140-age) × weight[kg]) / (72 × serum creatinine [mL/min]) × 0.85, if
female.
8. Adequate hematologic parameters:
1. Absolute neutrophil count (ANC) ≥1.0 × 10^9/L (growth factor support allowed)
2. Platelet count ≥100,000/mm^3 (100 × 10^9/L) (transfusion and/or growth factor
support allowed)
3. Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed)
9. Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be
less than or equal to 350 mg/dL
10. Minimum of 4 weeks since any major surgery, completion of radiation, and adequately
recovered from the acute toxicities of any prior therapy, including neuropathy, to
Grade ≤1
11. Male or 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 study medication
throughout 3 months after last dose of study medication 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 EOS treatment. A second form of birth control is required
even if she has had a tubal ligation.
2. Male patients must agree not to donate sperm and must practice abstinence or
agree to use a condom during sexual contact with a pregnant female or a female
of childbearing potential while participating in the study and throughout 3
months after last dose of study medication. A second form of birth control is
required even if he has undergone a successful vasectomy.
3. 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.
12. The patient or the patient's legal guardian(s) understand(s) and sign(s) the
informed consent
13. Willingness and ability to comply with scheduled visits, laboratory tests, and other
study procedures
14. 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 mTOR inhibitors including nab-sirolimus
Note: Patients who have previously received locoregional or liver-directed therapies
(radiofrequency or microwave ablation, transarterial chemoembolization, etc.) are
eligible to enroll in the study.
2. Patients with functional NETs who are experiencing uncontrolled symptoms attributed
to hormones and other vasoactive substances secreted by the tumor
3. Patients with inactivating TSC1 or TSC2 alterations (based on tissue or liquid NGS)
4. Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective
treatment, either ongoing or completed ≤7 days prior to enrollment
5. Patients who have any severe and/or uncontrolled medical or psychiatric conditions
or other conditions that could affect their participation including:
1. Known or suspected brain metastases
2. Severe heart disease defined as unstable angina pectoris, 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 that is
≤50% of normal predicted value and/or an O2 saturation ≤88% at rest on room air
(Note: Spirometry and pulmonary function tests 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 diagnosis. Controlled non-melanoma
skin cancers, carcinoma in situ of the cervix, resected incidental prostate
cancer, certain low-grade hematologic malignancies (eg, chronic lymphocytic
leukemia, 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
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hoag Memorial Hospital Presbyterian
Address:
City:
Newport Beach
Zip:
92663
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jason Ledesma
Email:
Jason.ledesma@haog.org
Investigator:
Last name:
Michael Demeure, MD
Email:
Principal Investigator
Facility:
Name:
Rocky Mountain Cancer Centers
Address:
City:
Denver
Zip:
80218
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jennifer Hedge
Email:
jennifer.hege@usoncology.com
Investigator:
Last name:
Allen Cohn, MD
Email:
Principal Investigator
Facility:
Name:
Texas Oncology
Address:
City:
Dallas
Zip:
75246
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christine Terraciano
Email:
christine.terraciano@usoncology.com
Investigator:
Last name:
Scott Paulson, MD
Email:
Principal Investigator
Facility:
Name:
Medical College of Wisconsin Cancer Center
Address:
City:
Milwaukee
Zip:
53226
Country:
United States
Status:
Recruiting
Contact:
Last name:
Barbara A Dion, CCRC
Phone:
414-805-4639
Email:
badion@mcw.edu
Investigator:
Last name:
Alexandria T Phan, MD
Email:
Principal Investigator
Start date:
November 7, 2023
Completion date:
December 8, 2025
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/NCT05997056
