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

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05103358
• Other study ID #: TSC-007
• Status: Recruiting
• Phase: Phase 2
• Start date: February 15, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: February 2024
• Source: Aadi Bioscience, Inc.
• Contact: Aadi Bioscience Medical Information
• Phone: 1-888-246-2234
• Email: MedInfo[@]aadibio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Aadi Bioscience, Inc.

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Puerto Rico, 

Outcome

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