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Active, not recruitingNCT05103358Updated Jun 3, 2024

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 interventional study of nab-sirolimus in Tumor, Tumor, Solid and Metastasis, sponsored by Aadi Bioscience, Inc.. Active, not recruiting at 166 sites in 3 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2024-06-03.

Sponsored by Aadi Bioscience, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
120
Allocation
Non-randomized
Ages
12 Years and older
Sex
All
01

Study 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

Read the detailed description

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.

02

Conditions studied

  • 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

Keywords

  • TSC1 gene
  • TSC2 gene
  • Tissue agnostic
  • Basket
  • nab-sirolimus
  • mTOR inhibitor
  • nanoparticle albumin bound
  • mammalian target of rapamycin
  • mechanistic target of rapamycin
  • tumor profile
  • tuberous sclerosis complex 1
  • tuberous sclerosis complex 2
  • mTOR
  • sirolimus
  • TSC1
  • TSC2
  • ABI-009
  • FYARRO
  • Precision
  • Precision 1
  • Pathogenic alterations
  • Pathogenic mutations
  • Inactivating mutations
03

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
120 participants (estimated)

Study arms

  • Experimental
    Arm A: Pathogenic inactivating TSC1 alterations

    Patients with pathogenic inactivating TSC1 alterations.

    Drug: nab-sirolimus

  • Experimental
    Arm B: Pathogenic inactivating TSC2 alterations

    Patients with pathogenic inactivating TSC2 alterations.

    Drug: nab-sirolimus

Interventions

  • Drugnab-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

    Also known as: ABI-009

05

What researchers measure

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

    Time frame: 9 months

Secondary outcomes

  1. Duration of response (DOR)

    Determined for patients with BOR of confirmed CR or PR (by IRR)

    Time frame: 9 months

  2. Disease control rate

    BOR of confirmed CR or PR (either of any duration) or stable disease (SD) following study treatment initiation (by IRR)

    Time frame: 9 months

  3. Time to response

    Time from first dose of study drug to initial measurement of CR or PR, where CR or PR is subsequently confirmed

    Time frame: 9 months

  4. Progression-free survival

    Number of months from study treatment initiation to the date of disease progression (by IRR) or death due to any cause

    Time frame: 9 months

  5. Overall survival

    Number of months from study treatment initiation to the date of death due to any cause

    Time frame: 24 months

  6. Patient-reported outcome

    Changes from baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire v3.0 (EORTC-QOQ-C30) scores

    Time frame: 9 months

  7. Incidence and severity of treatment-emergent and treatment-related adverse events (AEs)

    Incidence and severity of treatment-emergent and treatment-related AEs as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

    Time frame: 9 months

06

Study locations

166 sites
  • Alabama Oncology
    Birmingham, Alabama 35243, United States
  • Southern Cancer Center
    Mobile, Alabama 36607, United States
  • Arizona Oncology Associates
    Goodyear, Arizona 85395, United States
  • Honor Health
    Phoenix, Arizona 85016, United States
  • Arizona Oncology Associates
    Prescott Valley, Arizona 86301, United States
  • Yuma Regional Medical Center
    Yuma, Arizona 85364, United States
  • PCR Oncology
    Arroyo Grande, California 93420, United States
  • Nextgen Oncology
    Beverly Hills, California 90212, United States
  • City of Hope
    Duarte, California 91010, United States
  • Providence Medical Foundation (Fullerton)
    Fullerton, California 92835, United States
  • MemorialCare
    Long Beach, California 90806, United States
  • USC Norris Comprehensive Cancer Center
    Los Angeles, California 90033, United States
  • UCLA - Jonsson Comprehensive Cancer Center
    Los Angeles, California 90095, United States
  • Providence Medical Foundation (Napa)
    Napa, California 94558, United States
  • Hoag Memorial Hospital Presbyterian
    Newport Beach, California 92663, United States
  • Sharp HealthCare
    San Diego, California 92123, United States
  • UCSF Helen Diller Family Comprehensive Cancer Center
    San Francisco, California 94115, United States
  • Ridley-Tree Cancer Center
    Santa Barbara, California 93105, United States
  • Sarcoma Oncology Research Center
    Santa Monica, California 90403, United States
  • Providence Medical Foundation
    Santa Rosa, California 95403, United States
  • Stanford Cancer Center
    Stanford, California 94305, United States
  • The Oncology Institute of Hope & Innovation
    Whittier, California 90602, United States
  • Rocky Mountain Cancer Centers
    Aurora, Colorado 80012, United States
  • Rocky Mountain Cancer Centers
    Boulder, Colorado 80303, United States
  • Rocky Mountain Cancer Centers
    Colorado Springs, Colorado 80907, United States
  • Rocky Mountain Cancer Centers (Williams St)
    Denver, Colorado 80218, United States
  • Rocky Mountain Cancer Centers
    Denver, Colorado 80220, United States
  • Rocky Mountain Cancer Centers
    Lakewood, Colorado 80228, United States
  • Rocky Mountain Cancer Centers
    Littleton, Colorado 80120, United States
  • Rocky Mountain Cancer Centers
    Lone Tree, Colorado 80124, United States
  • Rocky Mountain Cancer Centers
    Longmont, Colorado 80501, United States
  • Rocky Mountain Cancer Centers
    Pueblo, Colorado 81008, United States
  • Rocky Mountain Cancer Centers
    Thornton, Colorado 80260, United States
  • Hartford Healthcare
    Hartford, Connecticut 06102, United States
  • Eastern Connecticut Hematology and Oncology
    Norwich, Connecticut 06360, United States
  • Florida Cancer Specialists - North Division
    Altamonte Springs, Florida 32701, United States
  • Florida Cancer Specialists - South Division
    Bonita Springs, Florida 34135, United States
  • Florida Cancer Specialists - South Division
    Bradenton, Florida 34205, United States
  • Florida Cancer Specialists - South Division
    Bradenton, Florida 34211, United States
  • Florida Cancer Specialists - North Division
    Brandon, Florida 33511, United States
  • Florida Cancer Specialists - South Division
    Cape Coral, Florida 33909, United States
  • Florida Cancer Specialists - North Division
    Clearwater, Florida 33761, United States
  • Cancer Specialist - East
    Daytona Beach, Florida 32117, United States
  • Holy Cross Hospital
    Fort Lauderdale, Florida 33308, United States
  • Florida Cancer Specialists South Division
    Fort Myers, Florida 33901, United States
  • Florida Cancer Specialists - South
    Fort Myers, Florida 33905, United States
  • Florida Cancer Specialists - South
    Fort Myers, Florida 33908, United States
  • Florida Cancer Specialists - North Division
    Gainesville, Florida 32605, United States
  • Cancer Specialists of North Florida
    Jacksonville, Florida 32256, United States
  • The Oncology Institute of Hope and Innovation
    Lakeland, Florida 33812, United States
  • TOI Florida
    Lakeland, Florida 33812, United States
  • Florida Cancer Specialists - North Division
    Largo, Florida 33770, United States
  • Florida Cancer Specialists - North Division
    Lecanto, Florida 34461, United States
  • Florida Cancer Specialists - South Division
    Naples, Florida 34102, United States
  • Florida Cancer Specialists - North Division
    Ocala, Florida 34474, United States
  • Ocala Oncology
    Ocala, Florida 34474, United States
  • Florida Cancer Specialists - North Division
    Orange City, Florida 32763, United States
  • Florida Cancer Specialists - North Division
    Orlando, Florida 32806, United States
  • Florida Cancer Specialists - South Division
    Port Charlotte, Florida 33980, United States
  • Florida Cancer Specialists and Research Institute - North Division
    Saint Petersburg, Florida 33705, United States
  • Florida Cancer Specialists - North
    Saint Petersburg, Florida 33707, United States
  • Florida Cancer Specialists - South Division
    Sarasota, Florida 34232, United States
  • Florida Cancer Specialists - South Division
    Sarasota, Florida 34236, United States
  • Florida Cancer Specialist - East
    Stuart, Florida 34994, United States
  • Florida Cancer Specialists - North Division
    Tampa, Florida 33607, United States
  • Florida Cancer Specialists - North Division
    Tavares, Florida 32778, United States
  • Florida Cancer Specialists - North Division
    Trinity, Florida 34655, United States
  • Florida Cancer Specialists - South Division
    Venice, Florida 34285, United States
  • Florida Cancer Specialists - South Division
    Venice, Florida 34292, United States
  • Florida Cancer Specialists - East
    Vero Beach, Florida 32960, United States
  • Florida Cancer Specialists - East
    Wellington, Florida 33414, United States
  • Florida Cancer Specialists - East
    West Palm Beach, Florida 33401, United States
  • Morehouse School of Medicine
    Atlanta, Georgia 30303, United States
  • Hawaii Cancer Center
    Honolulu, Hawaii 96813, United States
  • Hope and Healing Cancer Services
    Hinsdale, Illinois 60521, United States
  • Northwest Oncology and Hematology
    Rolling Meadows, Illinois 60008, United States
  • Urology of Indiana
    Carmel, Indiana 46032, United States
  • Fort Wayne Medical Oncology and Hematology
    Fort Wayne, Indiana 46804, United States
  • Goshen Health
    Goshen, Indiana 46526, United States
  • Our Lady of the Lake
    Baton Rouge, Louisiana 70817, United States
  • Pontchartrain
    Hammond, Louisiana 70403, United States
  • American Oncology Partners of Maryland PA (Center for Cancer & Blood Disorders)
    Bethesda, Maryland 20817, United States
  • Frederick Health
    Frederick, Maryland 21702, United States
  • Maryland Oncology Hematology
    Rockville, Maryland 20850, United States
  • Dana Farber Cancer Institute
    Boston, Massachusetts 02215, United States
  • Southcoast Centers for Cancer Care
    Fairhaven, Massachusetts 02719, United States
  • Barbara Ann Karmanos Cancer Institute
    Detroit, Michigan 48201, United States
  • Sparrow Hospital
    Lansing, Michigan 48912, United States
  • Minnesota Oncology Hematology
    Minneapolis, Minnesota 55404, United States
  • Central Care Cancer Center
    Bolivar, Missouri 65613, United States
  • Lake Regional
    Osage Beach, Missouri 65065, United States
  • Mosaic Life Care
    Saint Joseph, Missouri 64507, United States
  • Washington University School of Medicine
    Saint Louis, Missouri 63110, United States
  • Oncology Hematology Associates
    Springfield, Missouri 65807, United States
  • Nebraska Cancer Specialists
    Grand Island, Nebraska 68803, United States
  • Nebraska Methodist Hospital
    Omaha, Nebraska 68114, United States
  • OptumCare Cancer Care-Parent
    Las Vegas, Nevada 89102, United States
  • Comprehensive Cancer Centers of Nevada
    Las Vegas, Nevada 89169, United States
  • New Jersey Cancer Care and Blood Disorders
    Belleville, New Jersey 07109, United States
  • Englewood Hospital and Medical Center
    Englewood, New Jersey 07631, United States

Showing the first 100 of 166 sites across 3 countries.

07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT05103358
Lead sponsor
Aadi Bioscience, Inc.
Responsible party
Sponsor
First posted
Nov 2, 2021
Start date
Feb 15, 2022
Primary completion
Dec 31, 2024 (estimated)
Completion
Dec 31, 2025 (estimated)
Last update
Jun 3, 2024

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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