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

NCT ID: NCT05103358

Last Updated: 2024-06-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-15

Study Completion Date

2025-12-31

Brief Summary

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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

Detailed Description

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Study TSC-007 is a prospective phase 2, open-label, multi-institutional basket trial to determine the efficacy and safety profile of nab-sirolimus administered to patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 genes. Patients will be treated with single agent IV nab-sirolimus until disease progression, or unacceptable toxicity, or until in the opinion of the investigator the patient is no longer benefiting from therapy, or at patient discretion.

Conditions

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Tumor Tumor, Solid Metastasis Metastatic Cancer Cancer Cancer Metastatic Tumors Neoplasms Neoplasm Metastasis Solid Tumor Advanced Solid Tumor Advanced Cancer Malignant Solid Tumor Malignant Solid Neoplasm Malignant Neoplasm Malignant Tumor TSC TSC1 TSC2 Metastatic Solid Tumor Metastatic Neoplasm

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: Pathogenic inactivating TSC1 alterations

Patients with pathogenic inactivating TSC1 alterations.

Group Type EXPERIMENTAL

nab-sirolimus

Intervention Type DRUG

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

Arm B: Pathogenic inactivating TSC2 alterations

Patients with pathogenic inactivating TSC2 alterations.

Group Type EXPERIMENTAL

nab-sirolimus

Intervention Type DRUG

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

Interventions

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nab-sirolimus

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

Intervention Type DRUG

Other Intervention Names

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ABI-009

Eligibility Criteria

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Inclusion Criteria

1. 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.
2. 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.
3. 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.
4. Patients must have 1 or more measurable target lesions by computed tomography (CT) scan or magnetic resonance imaging (MRI) (RECIST v1.1).
5. Age: 12 years or older.
6. 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.
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 ≥30 mL/min, Cockcroft-Gault CCr = ((140-age) × weight\[kg\]) / (72 × SCr\[mL/min\]) × 0.85, if female
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 ≤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. 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 investigational product (IP) throughout 3 months after last dose of IP 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. 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 IP. A second form of birth control is required even if he has undergone a successful vasectomy.
13. The patient or the patient's parent(s) or legal guardian(s) understand(s) and sign(s) the informed consent.
14. Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures.

Exclusion Criteria

1. Prior treatment with an mTOR inhibitor, including nab-sirolimus.
2. Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective treatment, either ongoing or completed ≤7 days prior to enrollment.
3. Patients with primary brain tumors or PEComa.
4. 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 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.
5. 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.
6. Uncontrolled hypertension (systolic blood pressure ≥160 mm-Hg and/or diastolic blood pressure ≥100 mm Hg).
7. Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
8. 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.
9. Active Hepatitis B or Hepatitis C, with detectable viral load.
5. 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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Aadi Bioscience, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Alabama Oncology

Birmingham, Alabama, United States

Site Status

Southern Cancer Center

Mobile, Alabama, United States

Site Status

Arizona Oncology Associates

Goodyear, Arizona, United States

Site Status

Honor Health

Phoenix, Arizona, United States

Site Status

Arizona Oncology Associates

Prescott Valley, Arizona, United States

Site Status

Yuma Regional Medical Center

Yuma, Arizona, United States

Site Status

PCR Oncology

Arroyo Grande, California, United States

Site Status

Nextgen Oncology

Beverly Hills, California, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

Providence Medical Foundation (Fullerton)

Fullerton, California, United States

Site Status

MemorialCare

Long Beach, California, United States

Site Status

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UCLA - Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Providence Medical Foundation (Napa)

Napa, California, United States

Site Status

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status

Sharp HealthCare

San Diego, California, United States

Site Status

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Ridley-Tree Cancer Center

Santa Barbara, California, United States

Site Status

Sarcoma Oncology Research Center

Santa Monica, California, United States

Site Status

Providence Medical Foundation

Santa Rosa, California, United States

Site Status

Stanford Cancer Center

Stanford, California, United States

Site Status

The Oncology Institute of Hope & Innovation

Whittier, California, United States

Site Status

Rocky Mountain Cancer Centers

Aurora, Colorado, United States

Site Status

Rocky Mountain Cancer Centers

Boulder, Colorado, United States

Site Status

Rocky Mountain Cancer Centers

Colorado Springs, Colorado, United States

Site Status

Rocky Mountain Cancer Centers (Williams St)

Denver, Colorado, United States

Site Status

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Site Status

Rocky Mountain Cancer Centers

Lakewood, Colorado, United States

Site Status

Rocky Mountain Cancer Centers

Littleton, Colorado, United States

Site Status

Rocky Mountain Cancer Centers

Lone Tree, Colorado, United States

Site Status

Rocky Mountain Cancer Centers

Longmont, Colorado, United States

Site Status

Rocky Mountain Cancer Centers

Pueblo, Colorado, United States

Site Status

Rocky Mountain Cancer Centers

Thornton, Colorado, United States

Site Status

Hartford Healthcare

Hartford, Connecticut, United States

Site Status

Eastern Connecticut Hematology and Oncology

Norwich, Connecticut, United States

Site Status

Florida Cancer Specialists - North Division

Altamonte Springs, Florida, United States

Site Status

Florida Cancer Specialists - South Division

Bonita Springs, Florida, United States

Site Status

Florida Cancer Specialists - South Division

Bradenton, Florida, United States

Site Status

Florida Cancer Specialists - South Division

Bradenton, Florida, United States

Site Status

Florida Cancer Specialists - North Division

Brandon, Florida, United States

Site Status

Florida Cancer Specialists - South Division

Cape Coral, Florida, United States

Site Status

Florida Cancer Specialists - North Division

Clearwater, Florida, United States

Site Status

Cancer Specialist - East

Daytona Beach, Florida, United States

Site Status

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Site Status

Florida Cancer Specialists South Division

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists - South

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists - South

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists - North Division

Gainesville, Florida, United States

Site Status

Cancer Specialists of North Florida

Jacksonville, Florida, United States

Site Status

The Oncology Institute of Hope and Innovation

Lakeland, Florida, United States

Site Status

TOI Florida

Lakeland, Florida, United States

Site Status

Florida Cancer Specialists - North Division

Largo, Florida, United States

Site Status

Florida Cancer Specialists - North Division

Lecanto, Florida, United States

Site Status

Florida Cancer Specialists - South Division

Naples, Florida, United States

Site Status

Florida Cancer Specialists - North Division

Ocala, Florida, United States

Site Status

Ocala Oncology

Ocala, Florida, United States

Site Status

Florida Cancer Specialists - North Division

Orange City, Florida, United States

Site Status

Florida Cancer Specialists - North Division

Orlando, Florida, United States

Site Status

Florida Cancer Specialists - South Division

Port Charlotte, Florida, United States

Site Status

Florida Cancer Specialists - South Division

Sarasota, Florida, United States

Site Status

Florida Cancer Specialists - South Division

Sarasota, Florida, United States

Site Status

Florida Cancer Specialists and Research Institute - North Division

St. Petersburg, Florida, United States

Site Status

Florida Cancer Specialists - North

St. Petersburg, Florida, United States

Site Status

Florida Cancer Specialist - East

Stuart, Florida, United States

Site Status

Florida Cancer Specialists - North Division

Tampa, Florida, United States

Site Status

Florida Cancer Specialists - North Division

Tavares, Florida, United States

Site Status

Florida Cancer Specialists - North Division

Trinity, Florida, United States

Site Status

Florida Cancer Specialists - South Division

Venice, Florida, United States

Site Status

Florida Cancer Specialists - South Division

Venice, Florida, United States

Site Status

Florida Cancer Specialists - East

Vero Beach, Florida, United States

Site Status

Florida Cancer Specialists - East

Wellington, Florida, United States

Site Status

Florida Cancer Specialists - East

West Palm Beach, Florida, United States

Site Status

Morehouse School of Medicine

Atlanta, Georgia, United States

Site Status

Hawaii Cancer Center

Honolulu, Hawaii, United States

Site Status

Hope and Healing Cancer Services

Hinsdale, Illinois, United States

Site Status

Northwest Oncology and Hematology

Rolling Meadows, Illinois, United States

Site Status

Urology of Indiana

Carmel, Indiana, United States

Site Status

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, United States

Site Status

Goshen Health

Goshen, Indiana, United States

Site Status

Our Lady of the Lake

Baton Rouge, Louisiana, United States

Site Status

Pontchartrain

Hammond, Louisiana, United States

Site Status

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

Bethesda, Maryland, United States

Site Status

Frederick Health

Frederick, Maryland, United States

Site Status

Maryland Oncology Hematology

Rockville, Maryland, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Southcoast Centers for Cancer Care

Fairhaven, Massachusetts, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Sparrow Hospital

Lansing, Michigan, United States

Site Status

Minnesota Oncology Hematology

Minneapolis, Minnesota, United States

Site Status

Central Care Cancer Center

Bolivar, Missouri, United States

Site Status

Lake Regional

Osage Beach, Missouri, United States

Site Status

Mosaic Life Care

Saint Joseph, Missouri, United States

Site Status

Oncology Hematology Associates

Springfield, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Nebraska Cancer Specialists

Grand Island, Nebraska, United States

Site Status

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Site Status

OptumCare Cancer Care-Parent

Las Vegas, Nevada, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

New Jersey Cancer Care and Blood Disorders

Belleville, New Jersey, United States

Site Status

Englewood Hospital and Medical Center

Englewood, New Jersey, United States

Site Status

Summit Medical Group - NJ

Florham Park, New Jersey, United States

Site Status

Atlantic Health System - Morristown Medical Center

Morristown, New Jersey, United States

Site Status

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Site Status

HOACNY

East Syracuse, New York, United States

Site Status

Cayuga Medical Center

Ithaca, New York, United States

Site Status

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

New York, New York, United States

Site Status

Southeastern Medical Oncology

Goldsboro, North Carolina, United States

Site Status

Sanford Health-Fargo

Fargo, North Dakota, United States

Site Status

Aultman Medical Group

Canton, Ohio, United States

Site Status

TriHealth

Cincinnati, Ohio, United States

Site Status

University of Cincinnati (UC) - Cancer Institute

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

The Toledo Clinic

Toledo, Ohio, United States

Site Status

Oklahoma State University (OSU) - Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

Oklahoma Cancer Specialist

Tulsa, Oklahoma, United States

Site Status

Gettysburg-PCSRI

Gettysburg, Pennsylvania, United States

Site Status

Alliance Cancer Specialists

Langhorne, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Cancer Care Associates of York - Parent

York, Pennsylvania, United States

Site Status

Prisma Health Cancer Institute

Greenville, South Carolina, United States

Site Status

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Site Status

Sanford Health

Sioux Falls, South Dakota, United States

Site Status

Sarah Cannon and HCA Research Institute

Dickson, Tennessee, United States

Site Status

Sarah Cannon and HCA Research Institute

Franklin, Tennessee, United States

Site Status

Sarah Cannon and HCA Research Institute

Gallatin, Tennessee, United States

Site Status

West Cancer Center

Germantown, Tennessee, United States

Site Status

Sarah Cannon and HCA Research Institute

Henderson, Tennessee, United States

Site Status

Sarah Cannon and HCA Research Institute

Hermitage, Tennessee, United States

Site Status

Sarah Cannon and HCA Research Institute

Lebanon, Tennessee, United States

Site Status

Baptist Cancer Center

Memphis, Tennessee, United States

Site Status

Sarah Cannon and HCA Research Institute

Murfreesboro, Tennessee, United States

Site Status

Sarah Cannon and HCA Research Institute

Nashville, Tennessee, United States

Site Status

Sarah Cannon and HCA Research Institute

Nashville, Tennessee, United States

Site Status

Sarah Cannon and HCA Research Institute

Nashville, Tennessee, United States

Site Status

Sarah Cannon and HCA Research Institute

Nashville, Tennessee, United States

Site Status

Sarah Cannon and HCA Research Institute

Shelbyville, Tennessee, United States

Site Status

Sarah Cannon and HCA Research Institute

Smyrna, Tennessee, United States

Site Status

Mary Crowley Cancer Research

Dallas, Texas, United States

Site Status

Texas Oncology - DFW

Dallas, Texas, United States

Site Status

Texas Oncology

El Paso, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Oncology Consultants

Houston, Texas, United States

Site Status

Arizona Oncology Associates

Irving, Texas, United States

Site Status

Lumi Research

Kingwood, Texas, United States

Site Status

Texas Oncology Central-South

McAllen, Texas, United States

Site Status

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, United States

Site Status

Texas Oncology

Tyler, Texas, United States

Site Status

Community Cancer Trials of Utah

Ogden, Utah, United States

Site Status

Utah Cancer Specialists

Salt Lake City, Utah, United States

Site Status

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status

Hematology Oncology Associates of Fredericksburg

Fredericksburg, Virginia, United States

Site Status

Virginia Urology

Richmond, Virginia, United States

Site Status

University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Spokane Urology

Spokane, Washington, United States

Site Status

Cancer Care Northwest

Spokane, Washington, United States

Site Status

Northwest Medical Specialties

Tacoma, Washington, United States

Site Status

ThedaCare

Appleton, Wisconsin, United States

Site Status

Gunderson Health System

La Crosse, Wisconsin, United States

Site Status

University of Wisconsin - Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

Pan Oncology Trials, LLC

San Juan, , Puerto Rico

Site Status

Inje University Haeundae Paik Hospital

Busan, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Korea University Guro Hospital

Seoul, , South Korea

Site Status

Countries

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United States Puerto Rico South Korea

Other Identifiers

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TSC-007

Identifier Type: -

Identifier Source: org_study_id

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