None listed
Conditions
Brief summary
This study aims to find the safest and most effective dose of a new investigational drug called Sapu003 (Everolimus). In women with advanced or metastatic breast cancer that is hormone receptor-positive (HR+) and HER2-negative (HER2–), Sapu003 will be given together with exemestane (a hormone therapy). In other participants with advanced solid tumours such as kidney cancer, liver cancer, neuroendocrine tumours, or tuberous sclerosis complex–related tumours, Sapu003 will be given on its own. Who is it for? You may be eligible for this study if you are an adult aged 18 years or older with one of the following conditions: - Post-menopausal women with Stage 4/metastatic or locally advanced breast cancer that is HR+ and HER2–. - Adults with advanced or metastatic solid tumours including renal cell carcinoma (kidney cancer), hepatocellular carcinoma (liver cancer), neuroendocrine tumours, or tuberous sclerosis complex–related tumours. You may also be asked to complete additional health checks with a study doctor to determine if you are able to enrol in this study. Study details All participants who choose to enrol in this study will be allocated to a treatment group to receive a dose of Sapu003 (Everolimus) that will be given intravenously (via a vein) once a week for a 4-week cycle. Participants who don't experience any dangerous side effects will be asked to continue receiving Sapu003 each month for up to 6 months. - Women with HR+/HER2– breast cancer will also take a single oral dose of exemestane daily so that any drug interactions between exemestane and Sapu003 can be studied. - Participants with other advanced solid tumours will receive Sapu003 alone. Higher doses of Sapu003 may be studied if the initial participant group reports no dangerous side effects. Participants will also be asked to provide additional blood samples throughout the study and to report any side effects they experience while taking the study drugs. It is hoped this research will determine a safe dose of Sapu003 for future trials and to see whether the combination of Sapu003 and exemestane shows promise in controlling cancer spread in patients with HR+/HER- breast cancer who are also post-menopausal.
Interventions
The investigational intervention consists of Sapu003 (Everolimus) for Injection, administered intravenously over 30 minutes once weekly in 4-week (28-day) cycles. Dose escalation will follow the Bayesian Optimal Interval (BOIN) design to determine the Maximum Tolerated Dose (MTD), with planned dose levels of 5 mg/m², 7.5 mg/m², and 10 mg/m², and an optional –1 cohort at 3.5 mg/m² if required for safety. Treatment will continue for up to 6 months or until disease progression, unacceptable toxicit
The investigational intervention consists of Sapu003 (Everolimus) for Injection, administered intravenously over 30 minutes once weekly in 4-week (28-day) cycles. Dose escalation will follow the Bayesian Optimal Interval (BOIN) design to determine the Maximum Tolerated Dose (MTD), with planned dose levels of 5 mg/m², 7.5 mg/m², and 10 mg/m², and an optional –1 cohort at 3.5 mg/m² if required for safety. Treatment will continue for up to 6 months or until disease progression, unacceptable toxicity, or withdrawal of consent. Dose escalation/de-escalation decisions will be made at the end of each cohort based on the Bayesian Optimal Interval (BOIN) design. Separate cohorts of patients are enrolled at each dose level. All patients at a given dose level must complete one full cycle (4 weekly infusions) before the next cohort at the higher dose can be enrolled. Sapu003 will be reconstituted in 0.9% Sodium Chloride Injection, USP (4 mg/mL), diluted in 250 mL 0.9% Sodium Chloride, stored at 2–8°C, protected from light, and administered using amber-covered IV tubing. All participants will also receive exemestane 25 mg orally once daily throughout the study, administered continuously in combination with Sapu003 until disease progression, unacceptable toxicity, or withdrawal of consent. Exemestane is a steroidal aromatase inhibitor that irreversibly suppresses estrogen synthesis and represents the standard of care for HR+/HER2- advanced breast cancer after progression on non-steroidal aromatase inhibitors. Participants must also be on stable doses of metformin or statins prior to enrollment, as these agents are expected to provide synergistic effects by modulating mTOR signaling and tumor metabolism. Supportive medications, including antiemetics and G-CSF for neutropenia, are permitted. Adherence to the Exemestane doses is assessed indirectly through patient reporting and documentation of concomitant medications at study visits.
The investigational intervention consists of Sapu003 (Everolimus) for Injection, administered intravenously over 30 minutes once weekly in 4-week (28-day) cycles.
The study will enroll patients with advanced mTOR-sensitive solid tumors and will include two cohorts:
Cohort A: Patients with HR+/HER2-negative breast cancer receiving Sapu003 in combination with exemestane.
Cohort B: Patients with RCC, NETs, TSC-associated tumors, or HCC receiving Sapu003 as monotherapy.
Dose escalation will follow
The investigational intervention consists of Sapu003 (Everolimus) for Injection, administered intravenously over 30 minutes once weekly in 4-week (28-day) cycles. The study will enroll patients with advanced mTOR-sensitive solid tumors and will include two cohorts: Cohort A: Patients with HR+/HER2-negative breast cancer receiving Sapu003 in combination with exemestane. Cohort B: Patients with RCC, NETs, TSC-associated tumors, or HCC receiving Sapu003 as monotherapy. Dose escalation will follow the Bayesian Optimal Interval (BOIN) design to determine the Maximum Tolerated Dose (MTD), with planned dose levels of 5 mg/m², 7.5 mg/m², and 10 mg/m², and an optional –1 cohort at 3.5 mg/m² if required for safety. Treatment will continue for up to 6 months or until disease progression, unacceptable toxicity, or withdrawal of consent. Dose escalation/de-escalation decisions will be made at the end of each cohort based on the Bayesian Optimal Interval (BOIN) design. Separate cohorts of patients are enrolled at each dose level. All patients at a given dose level must complete one full cycle (4 weekly infusions) before the next cohort at the higher dose can be enrolled. Sapu003 will be reconstituted in 0.9% Sodium Chloride Injection, USP (4 mg/mL), diluted in 250 mL 0.9% Sodium Chloride, stored at 2–8°C, protected from light, and administered using amber-covered IV tubing. Participants in cohort A will also receive exemestane 25 mg orally once daily throughout the study, administered continuously in combination with Sapu003 until disease progression, unacceptable toxicity, or withdrawal of consent. Exemestane is a steroidal aromatase inhibitor that irreversibly suppresses estrogen synthesis and represents the standard of care for HR+/HER2- advanced breast cancer after progression on non-steroidal aromatase inhibitors. All participants must also be on stable doses of metformin or statins prior to enrollment, as these agents are expected to provide synergistic effects by modulating mTOR signaling and tumor metabolism. Supportive medications, including antiemetics and G-CSF for neutropenia, are permitted. Adherence to the Exemestane doses is assessed indirectly through patient reporting and documentation of concomitant medications at study visits.
Sponsors
Ingenu CRO Pty. Ltd
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Sex and Age: Postmenopausal women; defined as those 18 years of age or older exhibiting amenorrhea for more than or equal to 12 consecutive months without another pathophysiological cause 2. Female breast cancer patient who: • Has histologically or cytologically documented advanced (metastatic or unresctable) hormone receptor-positive, HER2 negative breast cancer (advanced HR+ BC) • Has stage IV or locally advanced breast cancer per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Seventh Edition; • Has failed any combination endocrine therapy or relapse within 6 months of adjuvant chemotherapy for metastatic or locally advanced disease. Prior therapy should have included a non-steroidal aromatase inhibitor unless clinically contraindicated; • Has agreed to participate in the study and signed the informed consent form prior to participation in any study activities. 3. Patients must be on stable doses of metformin or statin 4. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. 5. Life expectancy more than or equal to 3 months 6. Hematology/chemistry: Patient has adequate hematological, renal, and hepatic function as defined by the following Screening laboratory values obtained within 7 days prior to randomization and assessed based on local labs (patients should not have received a transfusion within 7 days before the Screening laboratory assessments): • Absolute neutrophil count (ANC) more than or equal to 2,000 cells/mm3 (2 x109/L) • Platelet count more than or equal to 100,000 cells/mm3 (100x109/L) • Hemoglobin more than or equal to 9 g/dL • Serum creatinine less than or equal to 1.5 x the upper limit of normal (ULN) • Total bilirubin less than or equal to 1.5 x ULN or direct bilirubin less than or equal to 1 x ULN for patients with total bilirubin levels > 1.5 ULN • AST (SGOT) / ALT (SGPT) less than or equal to 2.5 x ULN (less than or equal to 5 x ULN for patients with metastases.) • GFR more than or equal to 50 mL/min/1.73m2 by the CKD-EPI or MDRD formulas. 7. All other clinical laboratory values deemed as normal or not clinically significant by the Principal Investigator/Sub-Investigator. 8. This study enrolls only post-menopausal women, defined as those who have not experienced a menstrual period for at least 52 weeks or who have undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, bilateral tubal ligation). However, women who do not clearly meet these post-menopausal criteria will be excluded to ensure the study population is limited to non-childbearing participants. 9. Breastfeeding: Patients must be non-lactating. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding must be discontinued prior to the first dose of study drug. 10. Able and willing to adhere to all protocol requirements and study procedures throughout the course of the study. 11. Ability to comprehend and be informed of the nature of the study, as assessed by study clinic staff
Exclusion criteria
1. Patients with a history of other malignancies, except for adequately treated non-melanoma skin cancer, curatively treated in-situ carcinoma of the cervix, curatively treated in-situ carcinoma of the breast, or other solid tumors curatively treated with no evidence of disease for more than 5 years. 2. Patients who have not completely recovered from any toxicities from previous chemotherapy, hormone therapy, immunotherapy, or radiotherapies more than or equal to Grade 1 per NCI CTCAE version 5.0, with the exception of alopecia. 3. Patients who have received any of the following treatments within the specified timeframes prior to screening: - Prior chemotherapy within 30 days prior to screening (42 days for mitomycin C or nitrosoureas). - Prior immunotherapy, prior anti-tumor hormonal therapy, and prior radiotherapy within 30 days prior to screening. - Radiotherapy is not allowed during study. Administration of other chemotherapy, immunotherapy, or anti-tumor hormonal therapy during the study is not allowed. 4. Patient had major surgery within 30 days prior to randomization, or patient has not recovered from prior major surgery. 5. Sensory / Peripheral neuropathy of more than Grade 1 per NCI CTCAE version 5.0 at Screening. 6. Patients with active brain metastases. Patients with treated brain metastases are eligible provided they have no evidence of active brain disease and are off of definitive therapy (including steroids) at least 3 months prior to randomization. 7. Known history or presence of any clinically significant disease or condition other than cancer unless determined as not clinically significant by the Principal Investigator/Sub-Investigator. This includes, but is not limited to, the following: hepatic, renal/genitourinary, gastrointestinal (e.g., intra-abdominal inflammation), cardiovascular (e.g., congestive heart failure, ventricular arrhythmia, myocardial infarction, unstable angina pectoris), cerebrovascular, pulmonary (e.g., interstitial lung disease), endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological, or hematological (e.g., bleeding diathesis or coagulopathy). 8. History of difficulty with donating blood or difficulty in accessibility of central line. 9. Known history or presence of: • Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C (serology to confirm absence is required within 7 days prior to randomization and assessed based on local labs); • Alcohol abuse or dependence within one year prior to randomization; • Drug abuse or dependence (marijuana, amphetamines, barbiturates, cocaine, opiates and benzodiazepines); • Hypersensitivity or idiosyncratic reaction to everolimus, other rapamycin derivatives or its excipients • Severe allergic reactions (e.g., anaphylactic reactions, angioedema). 10. Patients may not participate in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or the use of investigational devices with therapeutic intent within 30 days prior to randomization and while enrolled in this study. Caution is recommended when administering Sapu003 and concomitantly with known substrates, PgP inhibitors, inhibitors, and inducers of the cytochrome P450 isoenzymes CYP2C8 and CYP3A4. 11. Use of any strong inhibitors of cytochrome P450 (CYP) enzymes (e.g., fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (e.g., barbiturates (phenobarbital), carbamazepine, phenytoin and rifampin), in the previous 14 days before randomization until the last blood draw in the study. 12. Acute active infection requiring antibiotics, antiviral agents, or antifungal agents within 14 days prior to randomization
Outcome results
None listed