NCT05103358|Active Not RecruitingPhase 2DMCFDA Drug

Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)

A Phase 2 Multi-center Open-label Basket Trial of Nab-sirolimus for Adult and Adolescent Patients With Malignant Solid Tumors Harboring Pathogenic Inactivating Alterations in TSC1 or TSC2 Genes.

Aadi Bioscience, Inc.ClinicalTrials.gov

Compare

1 other identifier

TSC-007

Study Type

interventional

Target

120

Locations

3 countries

Sites

166

Timeline

RegisteredNov 2021

StartedFeb 2022

CompletionDec 2025

Brief Summary

A Phase 2 multi-center open-label basket trial of nab-sirolimus for adult and adolescent patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 genes

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

120

participants targeted

Target at P50-P75 for phase_2

Timeline

Completed

Started Feb 2022

Typical duration for phase_2

Geographic Reach

3 countries

166 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3.9 years study duration

First Submitted

Initial submission to the registry

October 22, 2021

Completed

11 days until next milestone

First Posted

Study publicly available on registry

November 2, 2021

Completed

4 months until next milestone

Study Start

First participant enrolled

February 15, 2022

Completed

2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2024

Completed

1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2025

Completed

Last Updated

June 3, 2024

Status Verified

May 1, 2024

Enrollment Period

2.9 years

First QC Date

October 22, 2021

Last Update Submit

May 31, 2024

Conditions

Keywords

TSC1 geneTSC2 geneTissue agnosticBasketnab-sirolimusmTOR inhibitornanoparticle albumin boundmammalian target of rapamycinmechanistic target of rapamycintumor profiletuberous sclerosis complex 1tuberous sclerosis complex 2mTORsirolimusTSC1TSC2ABI-009FYARROPrecisionPrecision 1Pathogenic alterationsPathogenic mutationsInactivating mutations

Outcome Measures

Primary Outcomes (1)

Overall response rate (ORR)
ORR based on 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 disease progression as determined by IRR using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
9 months

Secondary Outcomes (7)

Duration of response (DOR)
9 months
Disease control rate
9 months
Time to response
9 months
Progression-free survival
9 months
Overall survival
24 months
+2 more secondary outcomes

Study Arms (2)

Arm A: Pathogenic inactivating TSC1 alterations

EXPERIMENTAL

Patients with pathogenic inactivating TSC1 alterations.

Drug: nab-sirolimus

Arm B: Pathogenic inactivating TSC2 alterations

EXPERIMENTAL

Patients with pathogenic inactivating TSC2 alterations.

Drug: nab-sirolimus

Interventions

nab-sirolimusDRUG

Prospective phase 2, open-label, multi-institutional basket trial to determine the efficacy and safety of nab-sirolimus administered by IV infusion to patients

Also known as: ABI-009

Arm A: Pathogenic inactivating TSC1 alterationsArm B: Pathogenic inactivating TSC2 alterations

Eligibility Criteria

Age12 Years+

Sexall

Healthy VolunteersNo

Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

Patients must have a malignant solid tumor with a pathogenic inactivating TSC1 or TSC2 alteration. Genetic alterations should be identified using NGS in tumor tissue or liquid biopsy).
Patients will be enrolled after the central evaluation of NGS report confirms eligibility.
Patients must have solid tumors that are metastatic or locally advanced where surgical resection is not an option or likely to result in severe morbidity.
Patients must have received all standard therapies appropriate for their tumor type and stage of disease or, in the opinion of the Investigator, the patient would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy, or the patient has no satisfactory alternative treatments.
Patients must have 1 or more measurable target lesions by computed tomography (CT) scan or magnetic resonance imaging (MRI) (RECIST v1.1).
Age: 12 years or older.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or Karnofsky Performance Status (KPS) ≥80 or Lansky play-performance scale for pediatric patients ≥80.
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 ≥30 mL/min, Cockcroft-Gault CCr = ((140-age) × weight\[kg\]) / (72 × SCr\[mL/min\]) × 0.85, if female
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)
+7 more criteria

You may not qualify if:

Prior treatment with an mTOR inhibitor, including nab-sirolimus.
Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective treatment, either ongoing or completed ≤7 days prior to enrollment.
Patients with primary brain tumors or PEComa.
Patients who have any severe and/or uncontrolled medical or psychiatric conditions or other conditions that could affect their participation including:
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 MRI scan should show no increase in brain lesion size/volume.
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.
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).
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 diagnosis. Note, controlled non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer, certain low grade hematologic malignancies (eg 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 mm-Hg and/or diastolic blood pressure ≥100 mm Hg).
Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
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.
Active Hepatitis B or Hepatitis C, with detectable viral load.
Regarding concomitant medications with significant CYP3A4 and P-gp interactions, discontinuation of strong inhibitors (eg, ketoconazole, itraconazole, voriconazole, erythromycin, clarithromycin, telithromycin, and others), strong inducers (eg, rifampin, rifabutin), and known CYP3A4 substrates with a narrow therapeutic window (eg, fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, or terfenadine) is required at least 5 half lives prior to receiving the first dose of nab-sirolimus, whichever is longer.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Aadi Bioscience, Inc.lead

Study Sites (166)

Alabama Oncology

Birmingham, Alabama, 35243, United States

Location

Southern Cancer Center

Mobile, Alabama, 36607, United States

Location

Arizona Oncology Associates

Goodyear, Arizona, 85395, United States

Location

Honor Health

Phoenix, Arizona, 85016, United States

Location

Arizona Oncology Associates

Prescott Valley, Arizona, 86301, United States

Location

Yuma Regional Medical Center

Yuma, Arizona, 85364, United States

Location

PCR Oncology

Arroyo Grande, California, 93420, United States

Location

Nextgen Oncology

Beverly Hills, California, 90212, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Providence Medical Foundation (Fullerton)

Fullerton, California, 92835, United States

Location

MemorialCare

Long Beach, California, 90806, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCLA - Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

Providence Medical Foundation (Napa)

Napa, California, 94558, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Sharp HealthCare

San Diego, California, 92123, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Ridley-Tree Cancer Center

Santa Barbara, California, 93105, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Providence Medical Foundation

Santa Rosa, California, 95403, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

The Oncology Institute of Hope & Innovation

Whittier, California, 90602, United States

Location

Rocky Mountain Cancer Centers

Aurora, Colorado, 80012, United States

Location

Rocky Mountain Cancer Centers

Boulder, Colorado, 80303, United States

Location

Rocky Mountain Cancer Centers

Colorado Springs, Colorado, 80907, United States

Location

Rocky Mountain Cancer Centers (Williams St)

Denver, Colorado, 80218, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80220, United States

Location

Rocky Mountain Cancer Centers

Lakewood, Colorado, 80228, United States

Location

Rocky Mountain Cancer Centers

Littleton, Colorado, 80120, United States

Location

Rocky Mountain Cancer Centers

Lone Tree, Colorado, 80124, United States

Location

Rocky Mountain Cancer Centers

Longmont, Colorado, 80501, United States

Location

Rocky Mountain Cancer Centers

Pueblo, Colorado, 81008, United States

Location

Rocky Mountain Cancer Centers

Thornton, Colorado, 80260, United States

Location

Hartford Healthcare

Hartford, Connecticut, 06102, United States

Location

Eastern Connecticut Hematology and Oncology

Norwich, Connecticut, 06360, United States

Location

Florida Cancer Specialists - North Division

Altamonte Springs, Florida, 32701, United States

Location

Florida Cancer Specialists - South Division

Bonita Springs, Florida, 34135, United States

Location

Florida Cancer Specialists - South Division

Bradenton, Florida, 34205, United States

Location

Florida Cancer Specialists - South Division

Bradenton, Florida, 34211, United States

Location

Florida Cancer Specialists - North Division

Brandon, Florida, 33511, United States

Location

Florida Cancer Specialists - South Division

Cape Coral, Florida, 33909, United States

Location

Florida Cancer Specialists - North Division

Clearwater, Florida, 33761, United States

Location

Cancer Specialist - East

Daytona Beach, Florida, 32117, United States

Location

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Florida Cancer Specialists South Division

Fort Myers, Florida, 33901, United States

Location

Florida Cancer Specialists - South

Fort Myers, Florida, 33905, United States

Location

Florida Cancer Specialists - South

Fort Myers, Florida, 33908, United States

Location

Florida Cancer Specialists - North Division

Gainesville, Florida, 32605, United States

Location

Cancer Specialists of North Florida

Jacksonville, Florida, 32256, United States

Location

The Oncology Institute of Hope and Innovation

Lakeland, Florida, 33812, United States

Location

TOI Florida

Lakeland, Florida, 33812, United States

Location

Florida Cancer Specialists - North Division

Largo, Florida, 33770, United States

Location

Florida Cancer Specialists - North Division

Lecanto, Florida, 34461, United States

Location

Florida Cancer Specialists - South Division

Naples, Florida, 34102, United States

Location

Florida Cancer Specialists - North Division

Ocala, Florida, 34474, United States

Location

Ocala Oncology

Ocala, Florida, 34474, United States

Location

Florida Cancer Specialists - North Division

Orange City, Florida, 32763, United States

Location

Florida Cancer Specialists - North Division

Orlando, Florida, 32806, United States

Location

Florida Cancer Specialists - South Division

Port Charlotte, Florida, 33980, United States

Location

Florida Cancer Specialists - South Division

Sarasota, Florida, 34232, United States

Location

Florida Cancer Specialists - South Division

Sarasota, Florida, 34236, United States

Location

Florida Cancer Specialists and Research Institute - North Division

St. Petersburg, Florida, 33705, United States

Location

Florida Cancer Specialists - North

St. Petersburg, Florida, 33707, United States

Location

Florida Cancer Specialist - East

Stuart, Florida, 34994, United States

Location

Florida Cancer Specialists - North Division

Tampa, Florida, 33607, United States

Location

Florida Cancer Specialists - North Division

Tavares, Florida, 32778, United States

Location

Florida Cancer Specialists - North Division

Trinity, Florida, 34655, United States

Location

Florida Cancer Specialists - South Division

Venice, Florida, 34285, United States

Location

Florida Cancer Specialists - South Division

Venice, Florida, 34292, United States

Location

Florida Cancer Specialists - East

Vero Beach, Florida, 32960, United States

Location

Florida Cancer Specialists - East

Wellington, Florida, 33414, United States

Location

Florida Cancer Specialists - East

West Palm Beach, Florida, 33401, United States

Location

Morehouse School of Medicine

Atlanta, Georgia, 30303, United States

Location

Hawaii Cancer Center

Honolulu, Hawaii, 96813, United States

Location

Hope and Healing Cancer Services

Hinsdale, Illinois, 60521, United States

Location

Northwest Oncology and Hematology

Rolling Meadows, Illinois, 60008, United States

Location

Urology of Indiana

Carmel, Indiana, 46032, United States

Location

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, 46804, United States

Location

Goshen Health

Goshen, Indiana, 46526, United States

Location

Our Lady of the Lake

Baton Rouge, Louisiana, 70817, United States

Location

Pontchartrain

Hammond, Louisiana, 70403, United States

Location

American Oncology Partners of Maryland PA (Center for Cancer & Blood Disorders)

Bethesda, Maryland, 20817, United States

Location

Frederick Health

Frederick, Maryland, 21702, United States

Location

Maryland Oncology Hematology

Rockville, Maryland, 20850, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Southcoast Centers for Cancer Care

Fairhaven, Massachusetts, 02719, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Sparrow Hospital

Lansing, Michigan, 48912, United States

Location

Minnesota Oncology Hematology

Minneapolis, Minnesota, 55404, United States

Location

Central Care Cancer Center

Bolivar, Missouri, 65613, United States

Location

Lake Regional

Osage Beach, Missouri, 65065, United States

Location

Mosaic Life Care

Saint Joseph, Missouri, 64507, United States

Location

Oncology Hematology Associates

Springfield, Missouri, 65807, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nebraska Cancer Specialists

Grand Island, Nebraska, 68803, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

OptumCare Cancer Care-Parent

Las Vegas, Nevada, 89102, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

New Jersey Cancer Care and Blood Disorders

Belleville, New Jersey, 07109, United States

Location

Englewood Hospital and Medical Center

Englewood, New Jersey, 07631, United States

Location

Summit Medical Group - NJ

Florham Park, New Jersey, 07932, United States

Location

Atlantic Health System - Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

HOACNY

East Syracuse, New York, 13057, United States

Location

Cayuga Medical Center

Ithaca, New York, 14850, United States

Location

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Southeastern Medical Oncology

Goldsboro, North Carolina, 27534, United States

Location

Sanford Health-Fargo

Fargo, North Dakota, 58102, United States

Location

Aultman Medical Group

Canton, Ohio, 44708, United States

Location

TriHealth

Cincinnati, Ohio, 45220, United States

Location

University of Cincinnati (UC) - Cancer Institute

Cincinnati, Ohio, 45627, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Toledo Clinic

Toledo, Ohio, 43623, United States

Location

Oklahoma State University (OSU) - Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oklahoma Cancer Specialist

Tulsa, Oklahoma, 74146, United States

Location

Gettysburg-PCSRI

Gettysburg, Pennsylvania, 17325, United States

Location

Alliance Cancer Specialists

Langhorne, Pennsylvania, 19047, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Cancer Care Associates of York - Parent

York, Pennsylvania, 17403, United States

Location

Prisma Health Cancer Institute

Greenville, South Carolina, 29605, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Sanford Health

Sioux Falls, South Dakota, 57117, United States

Location