Summary

Eligibility
for people ages 12 years and up (full criteria)
Location
at UCLA UCSF
Dates
study started
estimated completion
Principal Investigator
by Noah Federman, MD (ucla)Brian Schulte, MD (ucsf)
Headshot of Noah Federman
Noah Federman
Headshot of Brian Schulte
Brian Schulte

Description

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

Official Title

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

Details

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.

Keywords

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 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 ABI-009 FYARRO Precision Precision 1 Pathogenic alterations Pathogenic mutations Inactivating mutations Pathogenic inactivating TSC1 alterations Pathogenic inactivating TSC2 alterations

Eligibility

You can join if…

Open to people ages 12 years and up

  1. Patients must have a malignant solid tumor with a pathogenic inactivating TSC1 or TSC2 alteration. Genetic alterations should be identified in tumor tissue using NGS (ie, not by liquid biopsy alone).

• Patients will be enrolled after the central evaluation of NGS report confirms eligibility.

  1. Patients must provide baseline tumor tissue samples.
  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:
  8. Total bilirubin ≤1.5 × upper limit of normal (ULN) (unless due to Gilbert's syndrome, then ≤3 × ULN)
  9. Aspartate aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if attributable to liver metastases)
  10. Adequate renal function:
  11. Creatinine clearance ≥50 mL/min, Cockcroft-Gault CCr = ((140-age) x weight[kg]) / (72 x SCr[mL/min]) x 0.85, if female
  12. . Adequate hematologic parameters:
  13. Absolute neutrophil count (ANC) ≥1.0 × 109/L (growth factor support allowed)
  14. Platelet count ≥100,000/mm3 (100 × 109/L) (transfusion and/or growth factor support allowed)
  15. Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed)
  16. . Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be ≤350 mg/dL.
  17. . Minimum of 4 weeks since any 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 adequately recovered from the acute toxicities of any prior therapy, including neuropathy to Grade ≤1.
  18. . Male or non-pregnant and non-breastfeeding female:
  19. Females of child-bearing 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.
  20. 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 of IP. A second form of birth control is required even if he has undergone a successful vasectomy.
  21. . The patient or the patient's parent(s) or legal guardian(s) understand(s) and sign(s) the informed consent.
  22. . Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures.

You CAN'T join if...

  1. Prior treatment with an mTOR inhibitor, including nab-sirolimus.
  2. Recent infection requiring systemic (oral or IV) anti-infective treatment, either ongoing or completed ≤14 days prior to enrollment (except for uncomplicated urinary tract infection or upper respiratory tract infection).
  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:
  5. 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.
  6. 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.
  7. 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).
  8. 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 discussion with the medical monitor.
  9. Uncontrolled hypertension (systolic blood pressure ≥160 mm-Hg and/or diastolic blood pressure ≥100 mm Hg).
  10. Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
  11. 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.
  12. Active Hepatitis B or Hepatitis C, with detectable viral load.
  13. 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.

Locations

  • UCLA - Jonsson Comprehensive Cancer Center accepting new patients
    Los Angeles California 90095 United States
  • UCSF Helen Diller Family Comprehensive Cancer Center accepting new patients
    San Francisco California 94115 United States
  • Sarcoma Oncology Research Center accepting new patients
    Santa Monica California 90403 United States
  • Hoag Memorial Hospital Presbyterian accepting new patients
    Newport Beach California 92663 United States
  • Sharp HealthCare not yet accepting patients
    San Diego California 92123 United States
  • St. Joseph Heritage Health - Fullerton not yet accepting patients
    Fullerton California 92835 United States
  • MemorialCare not yet accepting patients
    Long Beach California 90806 United States
  • St Joseph Health Napa not yet accepting patients
    Napa California 94558 United States
  • City of Hope accepting new patients
    Duarte California 91010 United States
  • Stanford Cancer Center accepting new patients
    Stanford California 94305 United States

Lead Scientists at University of California Health

  • Noah Federman, MD (ucla)
    Dr. Noah Federman is the Director of the Pediatric Bone and Soft Tissue Sarcoma Program at UCLA, part of the UCLA Sarcoma Program and UCLA's Jonsson Comprehensive Cancer Center. Dr. Federman specializes in treating children, adolescents and young adults with these aggressive cancers.
  • Brian Schulte, MD (ucsf)
    Dr. Brian Schulte is a hematologist-oncologist who cares for patients with sarcomas, rare cancers that develop in connective tissues (such as bone, muscle or cartilage) and can affect people of all ages. Working as part of a multidisciplinary team, he strives to ensure patients receive the best possible comprehensive care.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Aadi Bioscience, Inc.
ID
NCT05103358
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 120 study participants
Last Updated