Cancer Clinical Trial
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.
Verified date | May 2024 |
Source | Aadi Bioscience, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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
Status | Active, not recruiting |
Enrollment | 120 |
Est. completion date | December 31, 2025 |
Est. primary completion date | December 31, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 12 Years and older |
Eligibility | 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, ß-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. |
Country | Name | City | State |
---|---|---|---|
Korea, Republic of | Inje University Haeundae Paik Hospital | Busan | |
Korea, Republic of | Asan Medical Center | Seoul | |
Korea, Republic of | Korea University Guro Hospital | Seoul | |
Korea, Republic of | Samsung Medical Center | Seoul | |
Korea, Republic of | Seoul National University Hospital | Seoul | |
Korea, Republic of | Severance Hospital, Yonsei University Health System | Seoul | |
Puerto Rico | Pan Oncology Trials, LLC | San Juan | |
United States | Florida Cancer Specialists - North Division | Altamonte Springs | Florida |
United States | ThedaCare | Appleton | Wisconsin |
United States | PCR Oncology | Arroyo Grande | California |
United States | Morehouse School of Medicine | Atlanta | Georgia |
United States | Rocky Mountain Cancer Centers | Aurora | Colorado |
United States | Our Lady of the Lake | Baton Rouge | Louisiana |
United States | New Jersey Cancer Care and Blood Disorders | Belleville | New Jersey |
United States | American Oncology Partners of Maryland PA (Center for Cancer & Blood Disorders) | Bethesda | Maryland |
United States | Nextgen Oncology | Beverly Hills | California |
United States | Alabama Oncology | Birmingham | Alabama |
United States | Central Care Cancer Center | Bolivar | Missouri |
United States | Florida Cancer Specialists - South Division | Bonita Springs | Florida |
United States | Dana Farber Cancer Institute | Boston | Massachusetts |
United States | Rocky Mountain Cancer Centers | Boulder | Colorado |
United States | Florida Cancer Specialists - South Division | Bradenton | Florida |
United States | Florida Cancer Specialists - South Division | Bradenton | Florida |
United States | Florida Cancer Specialists - North Division | Brandon | Florida |
United States | Roswell Park Comprehensive Cancer Center | Buffalo | New York |
United States | Aultman Medical Group | Canton | Ohio |
United States | Florida Cancer Specialists - South Division | Cape Coral | Florida |
United States | Urology of Indiana | Carmel | Indiana |
United States | TriHealth | Cincinnati | Ohio |
United States | University of Cincinnati (UC) - Cancer Institute | Cincinnati | Ohio |
United States | Florida Cancer Specialists - North Division | Clearwater | Florida |
United States | Cleveland Clinic | Cleveland | Ohio |
United States | Rocky Mountain Cancer Centers | Colorado Springs | Colorado |
United States | Mary Crowley Cancer Research | Dallas | Texas |
United States | Texas Oncology - DFW | Dallas | Texas |
United States | Cancer Specialist - East | Daytona Beach | Florida |
United States | Rocky Mountain Cancer Centers | Denver | Colorado |
United States | Rocky Mountain Cancer Centers (Williams St) | Denver | Colorado |
United States | Barbara Ann Karmanos Cancer Institute | Detroit | Michigan |
United States | Sarah Cannon and HCA Research Institute | Dickson | Tennessee |
United States | City of Hope | Duarte | California |
United States | HOACNY | East Syracuse | New York |
United States | Texas Oncology | El Paso | Texas |
United States | Englewood Hospital and Medical Center | Englewood | New Jersey |
United States | Virginia Cancer Specialists | Fairfax | Virginia |
United States | Southcoast Centers for Cancer Care | Fairhaven | Massachusetts |
United States | Sanford Health-Fargo | Fargo | North Dakota |
United States | Summit Medical Group - NJ | Florham Park | New Jersey |
United States | Holy Cross Hospital | Fort Lauderdale | Florida |
United States | Florida Cancer Specialists - South | Fort Myers | Florida |
United States | Florida Cancer Specialists - South | Fort Myers | Florida |
United States | Florida Cancer Specialists South Division | Fort Myers | Florida |
United States | Fort Wayne Medical Oncology and Hematology | Fort Wayne | Indiana |
United States | Sarah Cannon and HCA Research Institute | Franklin | Tennessee |
United States | Frederick Health | Frederick | Maryland |
United States | Hematology Oncology Associates of Fredericksburg | Fredericksburg | Virginia |
United States | Providence Medical Foundation (Fullerton) | Fullerton | California |
United States | Florida Cancer Specialists - North Division | Gainesville | Florida |
United States | Sarah Cannon and HCA Research Institute | Gallatin | Tennessee |
United States | West Cancer Center | Germantown | Tennessee |
United States | Gettysburg-PCSRI | Gettysburg | Pennsylvania |
United States | Southeastern Medical Oncology | Goldsboro | North Carolina |
United States | Arizona Oncology Associates | Goodyear | Arizona |
United States | Goshen Health | Goshen | Indiana |
United States | Nebraska Cancer Specialists | Grand Island | Nebraska |
United States | Prisma Health Cancer Institute | Greenville | South Carolina |
United States | Pontchartrain | Hammond | Louisiana |
United States | Hartford Healthcare | Hartford | Connecticut |
United States | Sarah Cannon and HCA Research Institute | Henderson | Tennessee |
United States | Sarah Cannon and HCA Research Institute | Hermitage | Tennessee |
United States | Hope and Healing Cancer Services | Hinsdale | Illinois |
United States | Hawaii Cancer Center | Honolulu | Hawaii |
United States | MD Anderson Cancer Center | Houston | Texas |
United States | Oncology Consultants | Houston | Texas |
United States | Arizona Oncology Associates | Irving | Texas |
United States | Cayuga Medical Center | Ithaca | New York |
United States | Cancer Specialists of North Florida | Jacksonville | Florida |
United States | Lumi Research | Kingwood | Texas |
United States | Gunderson Health System | La Crosse | Wisconsin |
United States | The Oncology Institute of Hope and Innovation | Lakeland | Florida |
United States | TOI Florida | Lakeland | Florida |
United States | Rocky Mountain Cancer Centers | Lakewood | Colorado |
United States | Alliance Cancer Specialists | Langhorne | Pennsylvania |
United States | Sparrow Hospital | Lansing | Michigan |
United States | Florida Cancer Specialists - North Division | Largo | Florida |
United States | Comprehensive Cancer Centers of Nevada | Las Vegas | Nevada |
United States | OptumCare Cancer Care-Parent | Las Vegas | Nevada |
United States | Sarah Cannon and HCA Research Institute | Lebanon | Tennessee |
United States | Florida Cancer Specialists - North Division | Lecanto | Florida |
United States | Rocky Mountain Cancer Centers | Littleton | Colorado |
United States | Rocky Mountain Cancer Centers | Lone Tree | Colorado |
United States | MemorialCare | Long Beach | California |
United States | Rocky Mountain Cancer Centers | Longmont | Colorado |
United States | UCLA - Jonsson Comprehensive Cancer Center | Los Angeles | California |
United States | USC Norris Comprehensive Cancer Center | Los Angeles | California |
United States | University of Wisconsin - Carbone Cancer Center | Madison | Wisconsin |
United States | Texas Oncology Central-South | McAllen | Texas |
United States | Baptist Cancer Center | Memphis | Tennessee |
United States | Minnesota Oncology Hematology | Minneapolis | Minnesota |
United States | Southern Cancer Center | Mobile | Alabama |
United States | Atlantic Health System - Morristown Medical Center | Morristown | New Jersey |
United States | Sarah Cannon and HCA Research Institute | Murfreesboro | Tennessee |
United States | Providence Medical Foundation (Napa) | Napa | California |
United States | Florida Cancer Specialists - South Division | Naples | Florida |
United States | Sarah Cannon and HCA Research Institute | Nashville | Tennessee |
United States | Sarah Cannon and HCA Research Institute | Nashville | Tennessee |
United States | Sarah Cannon and HCA Research Institute | Nashville | Tennessee |
United States | Sarah Cannon and HCA Research Institute | Nashville | Tennessee |
United States | David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center | New York | New York |
United States | Hoag Memorial Hospital Presbyterian | Newport Beach | California |
United States | Eastern Connecticut Hematology and Oncology | Norwich | Connecticut |
United States | Florida Cancer Specialists - North Division | Ocala | Florida |
United States | Ocala Oncology | Ocala | Florida |
United States | Community Cancer Trials of Utah | Ogden | Utah |
United States | Oklahoma State University (OSU) - Stephenson Cancer Center | Oklahoma City | Oklahoma |
United States | Nebraska Methodist Hospital | Omaha | Nebraska |
United States | Florida Cancer Specialists - North Division | Orange City | Florida |
United States | Florida Cancer Specialists - North Division | Orlando | Florida |
United States | Lake Regional | Osage Beach | Missouri |
United States | Thomas Jefferson University | Philadelphia | Pennsylvania |
United States | Honor Health | Phoenix | Arizona |
United States | Florida Cancer Specialists - South Division | Port Charlotte | Florida |
United States | Arizona Oncology Associates | Prescott Valley | Arizona |
United States | Rocky Mountain Cancer Centers | Pueblo | Colorado |
United States | Virginia Urology | Richmond | Virginia |
United States | Maryland Oncology Hematology | Rockville | Maryland |
United States | Northwest Oncology and Hematology | Rolling Meadows | Illinois |
United States | Mosaic Life Care | Saint Joseph | Missouri |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | Florida Cancer Specialists - North | Saint Petersburg | Florida |
United States | Florida Cancer Specialists and Research Institute - North Division | Saint Petersburg | Florida |
United States | Utah Cancer Specialists | Salt Lake City | Utah |
United States | South Texas Accelerated Research Therapeutics (START) | San Antonio | Texas |
United States | Sharp HealthCare | San Diego | California |
United States | UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California |
United States | Ridley-Tree Cancer Center | Santa Barbara | California |
United States | Sarcoma Oncology Research Center | Santa Monica | California |
United States | Providence Medical Foundation | Santa Rosa | California |
United States | Florida Cancer Specialists - South Division | Sarasota | Florida |
United States | Florida Cancer Specialists - South Division | Sarasota | Florida |
United States | University of Washington Cancer Consortium | Seattle | Washington |
United States | Sarah Cannon and HCA Research Institute | Shelbyville | Tennessee |
United States | Avera Cancer Institute | Sioux Falls | South Dakota |
United States | Sanford Health | Sioux Falls | South Dakota |
United States | Sarah Cannon and HCA Research Institute | Smyrna | Tennessee |
United States | Cancer Care Northwest | Spokane | Washington |
United States | Spokane Urology | Spokane | Washington |
United States | Oncology Hematology Associates | Springfield | Missouri |
United States | Stanford Cancer Center | Stanford | California |
United States | Florida Cancer Specialist - East | Stuart | Florida |
United States | Northwest Medical Specialties | Tacoma | Washington |
United States | Florida Cancer Specialists - North Division | Tampa | Florida |
United States | Florida Cancer Specialists - North Division | Tavares | Florida |
United States | Rocky Mountain Cancer Centers | Thornton | Colorado |
United States | The Toledo Clinic | Toledo | Ohio |
United States | Florida Cancer Specialists - North Division | Trinity | Florida |
United States | Oklahoma Cancer Specialist | Tulsa | Oklahoma |
United States | Texas Oncology | Tyler | Texas |
United States | Florida Cancer Specialists - South Division | Venice | Florida |
United States | Florida Cancer Specialists - South Division | Venice | Florida |
United States | Florida Cancer Specialists - East | Vero Beach | Florida |
United States | Florida Cancer Specialists - East | Wellington | Florida |
United States | Florida Cancer Specialists - East | West Palm Beach | Florida |
United States | The Oncology Institute of Hope & Innovation | Whittier | California |
United States | Cancer Care Associates of York - Parent | York | Pennsylvania |
United States | Yuma Regional Medical Center | Yuma | Arizona |
Lead Sponsor | Collaborator |
---|---|
Aadi Bioscience, Inc. |
United States, Korea, Republic of, Puerto Rico,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Duration of response (DOR) | Determined for patients with BOR of confirmed CR or PR (by IRR) | 9 months | |
Secondary | Disease control rate | BOR of confirmed CR or PR (either of any duration) or stable disease (SD) following study treatment initiation (by IRR) | 9 months | |
Secondary | Time to response | Time from first dose of study drug to initial measurement of CR or PR, where CR or PR is subsequently confirmed | 9 months | |
Secondary | Progression-free survival | Number of months from study treatment initiation to the date of disease progression (by IRR) or death due to any cause | 9 months | |
Secondary | Overall survival | Number of months from study treatment initiation to the date of death due to any cause | 24 months | |
Secondary | 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 | 9 months | |
Secondary | 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 | 9 months |
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