RECRUITING

Dose-escalation Study to Assess Safety and Pharmacokinetics of Nab-Sirolimus in Patients With Locally Advanced or Metastatic Solid Tumors and Moderate Liver Impairment

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a phase 1, multi-center, open-label, dose-escalation study of nab-sirolimus in adult patients with locally advanced or metastatic solid tumors and moderate hepatic impairment or normal hepatic function.

Official Title

A Phase 1, Open-label, Dose-escalation Study to Assess Safety and Pharmacokinetics of Nab-Sirolimus in Patients With Locally Advanced or Metastatic Solid Tumors and Moderate Liver Impairment

Quick Facts

Study Start:2022-11-23

Study Completion:2025-04-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05661461

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* For All Patients 1. Willing and able to provide informed consent and comply with protocol requirements for the duration of the study. 2. Male or female patients at least 18 years of age at the time of signing the informed consent form. 3. Histologically confirmed locally advanced or metastatic solid tumors that is measurable or non-measurable. 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. 5. Adequate hematologic counts: * Absolute neutrophil count (ANC) ≥1.0 × 109 /L (growth factor support allowed) * Platelet count ≥75,000/mm 3 (75 × 10 9 /L) (transfusion and/or growth factor support allowed) * Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed) 6. Creatinine clearance ≥30 mL/min as assessed by the Cockcroft-Gault equation: 7. Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be 8. Male or non-pregnant and non-breastfeeding female: * Females of child-bearing potential must agree to use highly effective contraception or abstinence without interruption from 28 days prior to first dose throughout 3 months after last dose and have a negative pregnancy test (urine or serum) result at screening and after the end of study treatment. A second form of birth control is required even if she has had a tubal ligation. * Male patients 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. A second form of birth control is required even if he has undergone a successful vasectomy. 9. Minimum of 4 weeks since major surgery, completion of radiation, or completion of all prior systemic anticancer therapy, or at least 5 half-lives if the prior therapy is a single agent small-molecule therapeutic, and in either case adequately recovered from the acute toxicities of any prior therapy (including neuropathy) to Grade ≤1. For Patients with Normal Hepatic Function 10. Normal hepatic function (total bilirubin ≤ upper limit of normal \[ULN\] and aspartate aminotransferase \[AST\] ≤ULN). For Patients with Moderate Hepatic Impairment 11. Moderate hepatic impairment (total bilirubin 1.5-3.0 × ULN and any level of AST)	1. Received prior treatment with an mTOR inhibitor within 4 weeks prior to first dose. 2. Patients who have any severe and/or uncontrolled medical or psychiatric conditions or other conditions that could affect their participation including: 1. Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, untreated brain metastases or symptomatic or unstable brain metastases. Note: Patients with stable brain metastases (defined as asymptomatic or no requirement for high-dose \[defined as dexamethasone 10 mg daily or higher\] or increasing dose of systemic corticosteroids) and without imminent need of radiation therapy are eligible. If applicable, patients must have completed brain radiation therapy and recovered adequately from any associated toxicity and/or complications prior to eligibility assessment. For patients who have received prior radiation therapy, post-treatment magnetic resonance imaging (MRI) scan should show no increase in brain lesion size/volume. 2. Unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association, NYHA class III or IV), myocardial infarction ≤6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease. 3. Pre-existing severely impaired lung function. If a patient has a pre-existing pulmonary condition, eligible patients should have a spirometry and diffusing capacity for carbon monoxide (DLCO) that is \>50% of the normal predicted value and/or O2 saturation that is \>88% at rest on room air (Note: spirometry and pulmonary function tests \[PFTs\] 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. Note, controlled non melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer, or other adequately treated carcinoma-in-situ may be eligible, after documented discussion with the Medical Monitor. 5. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg). 6. Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension. 7. Individuals with known human immunodeficiency virus (HIV) infection are excluded from this study as combination antiretroviral therapy could potentially result in significant pharmacokinetic interactions. In addition, these individuals are at increased risk of serious infections due to the immunosuppressive effects of mTOR inhibition. 8. Active Hepatitis B or Hepatitis C, with detectable viral load. Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. 3. Have active severe (Grade ≥3) infection requiring intravenous (IV) antibiotics (contact medical monitor for clarification). 4. High-dose systemic corticosteroids (\>10 mg of prednisone or its equivalent) are not permitted within 2 weeks of first dose. However, inhaled, intranasal, intra articular, and topical steroids are allowed. 5. Have a history of Gilbert's disease. 6. Any condition that in the opinion of the Investigator would place the patient at an unacceptable risk or cause the patient to be unlikely to fully participate or comply with study procedures. 7. Had a clinical exacerbation of liver disease within the 2-week period prior to first dose (ie, abdominal pain, nausea, vomiting, anorexia, or fever). 8. Have clinically demonstrable, tense ascites. 9. Had evidence of acute viral hepatitis within 1 month prior to first dose. 10. Have evidence of hepatorenal syndrome. 11. Have a transjugular intrahepatic portosystemic shunt. 12. Have active stage 3 or 4 encephalopathy.

Inclusion Criteria

Exclusion Criteria

* For All Patients
1. Willing and able to provide informed consent and comply with protocol requirements for the duration of the study.
2. Male or female patients at least 18 years of age at the time of signing the informed consent form.
3. Histologically confirmed locally advanced or metastatic solid tumors that is measurable or non-measurable.
4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
5. Adequate hematologic counts:
* Absolute neutrophil count (ANC) ≥1.0 × 109 /L (growth factor support allowed)
* Platelet count ≥75,000/mm 3 (75 × 10 9 /L) (transfusion and/or growth factor support allowed)
* Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed)
6. Creatinine clearance ≥30 mL/min as assessed by the Cockcroft-Gault equation:
7. Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be
8. Male or non-pregnant and non-breastfeeding female:
* Females of child-bearing potential must agree to use highly effective contraception or abstinence without interruption from 28 days prior to first dose throughout 3 months after last dose and have a negative pregnancy test (urine or serum) result at screening and after the end of study treatment. A second form of birth control is required even if she has had a tubal ligation.
* Male patients 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. A second form of birth control is required even if he has undergone a successful vasectomy.
9. Minimum of 4 weeks since major surgery, completion of radiation, or completion of all prior systemic anticancer therapy, or at least 5 half-lives if the prior therapy is a single agent small-molecule therapeutic, and in either case adequately recovered from the acute toxicities of any prior therapy (including neuropathy) to Grade ≤1. For Patients with Normal Hepatic Function
10. Normal hepatic function (total bilirubin ≤ upper limit of normal \[ULN\] and aspartate aminotransferase \[AST\] ≤ULN). For Patients with Moderate Hepatic Impairment
11. Moderate hepatic impairment (total bilirubin 1.5-3.0 × ULN and any level of AST)

1. Received prior treatment with an mTOR inhibitor within 4 weeks prior to first dose.
2. Patients who have any severe and/or uncontrolled medical or psychiatric conditions or other conditions that could affect their participation including:
1. Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, untreated brain metastases or symptomatic or unstable brain metastases. Note: Patients with stable brain metastases (defined as asymptomatic or no requirement for high-dose \[defined as dexamethasone 10 mg daily or higher\] or increasing dose of systemic corticosteroids) and without imminent need of radiation therapy are eligible. If applicable, patients must have completed brain radiation therapy and recovered adequately from any associated toxicity and/or complications prior to eligibility assessment. For patients who have received prior radiation therapy, post-treatment magnetic resonance imaging (MRI) scan should show no increase in brain lesion size/volume.
2. Unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association, NYHA class III or IV), myocardial infarction ≤6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.
3. Pre-existing severely impaired lung function. If a patient has a pre-existing pulmonary condition, eligible patients should have a spirometry and diffusing capacity for carbon monoxide (DLCO) that is \>50% of the normal predicted value and/or O2 saturation that is \>88% at rest on room air (Note: spirometry and pulmonary function tests \[PFTs\] 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. Note, controlled non melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer, or other adequately treated carcinoma-in-situ may be eligible, after documented discussion with the Medical Monitor.
5. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg).
6. Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
7. Individuals with known human immunodeficiency virus (HIV) infection are excluded from this study as combination antiretroviral therapy could potentially result in significant pharmacokinetic interactions. In addition, these individuals are at increased risk of serious infections due to the immunosuppressive effects of mTOR inhibition.
8. Active Hepatitis B or Hepatitis C, with detectable viral load. Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients.
3. Have active severe (Grade ≥3) infection requiring intravenous (IV) antibiotics (contact medical monitor for clarification).
4. High-dose systemic corticosteroids (\>10 mg of prednisone or its equivalent) are not permitted within 2 weeks of first dose. However, inhaled, intranasal, intra articular, and topical steroids are allowed.
5. Have a history of Gilbert's disease.
6. Any condition that in the opinion of the Investigator would place the patient at an unacceptable risk or cause the patient to be unlikely to fully participate or comply with study procedures.
7. Had a clinical exacerbation of liver disease within the 2-week period prior to first dose (ie, abdominal pain, nausea, vomiting, anorexia, or fever).
8. Have clinically demonstrable, tense ascites.
9. Had evidence of acute viral hepatitis within 1 month prior to first dose.
10. Have evidence of hepatorenal syndrome.
11. Have a transjugular intrahepatic portosystemic shunt.
12. Have active stage 3 or 4 encephalopathy.

Contacts and Locations

Study Contact

Aadi Medical Information

CONTACT

1-888-246-2234

MedInfo@aadibio.com

Study Locations (Sites)

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229

United States

START Mountain Region

West Valley City, Utah, 84119

United States

Collaborators and Investigators

Sponsor: Aadi Bioscience, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-11-23

Study Completion Date2025-04-01

Study Record Updates

Study Start Date2022-11-23

Study Completion Date2025-04-01

Terms related to this study

Additional Relevant MeSH Terms

Tumor, Solid
Tumor
Advanced Solid Tumor