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A Study of Safety and Efficacy of Sirolimus for Injection (Albumin-bound) in Patients With Advanced Malignant Perivascular Epithelioid Cell Tumor (PEComa)

Primary Purpose

Advanced Malignant Perivascular Epithelioid Cell Tumor (PEComa)

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Sirolimus for Injection (Albumin Bound)
Sponsored by
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Malignant Perivascular Epithelioid Cell Tumor (PEComa)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Aged 18 years or older, and Phase Ⅰb: Patients with histologically confirmed diagnosis of advanced soft tissue sarcomas (including malignant PEComa, accounting for at least 1/2) have failed standard treatment (disease progression or relapse or intolerance to chemotherapy, radiotherapy, targeted therapy, etc.) or lack effective treatment; Phase Ⅱ: Patients must have a histologically confirmed diagnosis of malignant PEComa that is either metastatic or locally advanced and for which surgery is not a recommended option. [Malignant PEComas displaying 2 or more of the features of large size (> 5 cm), infiltrative growth, high nuclear grade, cellular necrosis, mitoses ≥1/50 high power field (HPF), or vascular invasion] At least 1 measurable lesion as defined by RECIST 1.1. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Life expectancy >3 months. Patient must have the following biological parameters levels at screening (without blood transfusion, EPO, G-CSF and other medical support within14 days prior to screening tests): Blood tests: Absolute neutrophil count (ANC) ≥1.5 × 10^9/L; Platelet count ≥100 × 10^9/L; Hemoglobin ≥90 g/L; Renal function tests: serum creatinine ≤1.5 x upper limit of normal (ULN); Liver function tests: Total bilirubin ≤1.5 x ULN (Patients with liver metastases, bile duct obstruction, or confirmed Gilbert syndrome: ≤ 3×ULN); AST and ALT ≤2.5 x ULN (≤5 x ULN if attributable to liver metastases); Blood clotting function tests: INR or PT ≤ 1.5 × ULN; APTT≤ 1.5 × ULN; Fasting serum triglycerides<300 mg/dL(3.42 mmol/L), fasting serum cholesterol < 350 mg/dL ( 9.07mmol/L; ). Fasting blood glucose (FPG) < 7.8 mmol/L and HbA1c < 8%. Women of child-bearing potential, or men whose partners are women of childbearing age must agree to use reliable contraceptive methods during the trial period and at least 6 months after the last administration; women of childbearing age must have a negative serum pregnancy test within 7 days prior to the first administration, should not be breast feeding. Patients must give informed consent to the study prior to the trial and voluntarily sign informed consent form. Exclusion Criteria: Anti-tumor therapy such as chemotherapy, radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy within 4 weeks prior to the first dose of study drug, with the following special requirements: Nitrosoureas (eg, carmustine, lomustine, etc.) or mitomycin C within 6 weeks prior to the first dose of study drug; Oral fluorouracils and small molecule targeted drugs within 2 weeks or 5 half-lives (whichever is longer) before the first dose of study drug; Traditional Chinese medicines with anti-tumor indications within 2 weeks prior to the first dose of study drug; Received other unmarketed clinical investigational drug within 4 weeks prior to the first dose of study drug. Major surgical procedures within 4 weeks prior to the first dose of study drug or not fully recovered from any previous invasive procedures. Received systemic glucocorticoids (prednisone > 10 mg/day or equivalent doses) or other immunosuppressive therapy within 2 weeks prior to the first dose of the study drug [with the following exceptions: treatment with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term use of glucocorticoids for prophylaxis (eg, prevention of contrast allergy)]. Infection that required systemic anti-infective therapy (oral or IV) within 2 weeks before enrollment. Inactivated or live attenuated vaccine or novel coronavirus vaccine within 30 days before the first dose. Use of strong inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study drug, or requiring concomitant treatment during the study. History of other malignancies within 5 years prior to the first dose of the study drug, except in the following cases: cured basal cell or squamous cell skin cancer, superficial bladder cancer, prostatic carcinoma in situ, carcinoma in situ of the cervix, breast carcinoma in situ, etc., or locally curable cancer that has been disease-free for 5 years; Liver-directed therapy is required within 2 months of enrollment. Prior treatment with radiotherapy (including radio-labeled spheres and/or cyberknife, hepatic arterial embolization (with or without chemotherapy) or cyrotherapy/ablation) is allowed if these therapies does not affect the areas of measurable disease being used for this protocol. History of serious cardiovascular disease, such as severe heart rhythm or conduction abnormalities (ventricular arrhythmias requiring clinical intervention, grade Ⅱ or Ш atrioventricular block, etc.). History of myocardial infarction, unstable angina, heart failure, New York College of Cardiology (NYHA) grade Ⅱ and above, and coronary artery bypass surgery within 6 months before the first dose of the study drug; Left ventricular ejection fraction (LVEF) < 50%, QTcF > 450 msec (male) or female QTcF > 470 msec (female), etc. Unresolved toxicity from prior anti-tumor therapy greater than Grade 1 as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.(except for alopecia and any other toxicities that have no safety risk judged by the investigator). Known active uncontrolled or symptomatic central nervous system (CNS) metastases, or other evidence of uncontrollable central nervous system metastases or meningeal metastases that not eligible for inclusion determined by the investigator. Hydrothorax, ascites or pericardial effusion with clinical symptoms or required symptomatic treatment. Patients with angiomyolipoma(AML) or lymphangioleiomyomatosis (LAM). History of serious lung disease, such as interstitial lung disease and/or pneumonitis, or pulmonary hypertension, or pre-existing severely impaired lung function. Pre-existing thyroid abnormality is allowed provided thyroid function can be controlled with medication. Known hypersensitivity or intolerance to any ingredient in the study drug. History of autoimmune disease (except tuberous sclerosis), immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency disease, or history of organ transplantation. Active Hepatitis B or Hepatitis C, or active syphilis infection Active Hepatitis B: HBsAg-positive with HBV DNA titer ≥ 1 × 10^3 IU/mL; Patients are eligible for enrollment if they are HBsAg positive with peripheral blood HBV-DNA < 1 × 10^3 IU/mL if, in the opinion of the investigator, the patient's chronic hepatitis B is in a stable phase and does not increase the subject's risk. Active Hepatitis C: HCV antibodies -positive with HCV RNA-positive; Active syphilis infection: Treponema pallidum antibodies (RPR or TRUST)-positive or presence of syphilis infection requiring systemic therapy. Severe concomitant diseases that endanger patient safety, interfere the compliance of the study procedure (such as uncontrollable hypertension, active gastrointestinal bleeding, etc.) or other reasons that make the patient inappropriate for entry into this study.

Sites / Locations

  • Beijing Jishuitan HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sirolimus for Injection (Albumin-bound)

Arm Description

Sirolimus for injection (Albumin-bound) will be administered intravenously on day 1and day 8 every 21 days (a cycle).

Outcomes

Primary Outcome Measures

AE and SAE occurrence and frequency in phase Ⅰb
Dose-limiting toxicities (DLT)
Maximum tolerated dose (MTD)
Recommended phase 2 dose (RP2D)
Overall response rate (ORR) in phase Ⅱ

Secondary Outcome Measures

Overall response rate (ORR) in phase Ⅰb
Disease Control Rate (DCR)
Duration of Response (DOR)
Progression-free Survival (PFS)
Overall survival (OS)
AE and SAE occurrence and frequency in phase Ⅱ
Area under the plasma concentration versus time curve (AUC)
Peak Plasma Concentration (Cmax)
Peak time (Tmax)
Terminal half-life (t½)

Full Information

First Posted
November 14, 2022
Last Updated
November 23, 2022
Sponsor
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05625919
Brief Title
A Study of Safety and Efficacy of Sirolimus for Injection (Albumin-bound) in Patients With Advanced Malignant Perivascular Epithelioid Cell Tumor (PEComa)
Official Title
A Phase Ⅰb/Ⅱ Multi-center Study of Safety and Efficacy of Sirolimus for Injection (Albumin-bound) in Patients With Advanced Malignant Perivascular Epithelioid Cell Tumor (PEComa)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 8, 2022 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a phase Ⅰb/Ⅱ multi-center study of safety and efficacy of Sirolimus for Injection (Albumin-bound) in patients with advanced malignant perivascular epithelioid cell tumor (PEComa).
Detailed Description
This is a non-randomized, multi-center, open-label, Phase Ⅰb/Ⅱ clinical trial. For phase Ⅰb, patients must have a histologically confirmed diagnosis of advanced soft tissue sarcomas (including malignant PEComa, accounting for at least 1/2) that have failed standard treatment (disease progression or relapse or intolerance, such as chemotherapy, radiotherapy, targeted therapy, etc.) or lack effective treatment. The recommended phase II dose (RP2D) will be determined in phase Ⅰb. For phase Ⅱ, patients must have a histologically confirmed diagnosis of malignant PEComa that is either metastatic or locally advanced and for which surgery is not a recommended option. Phase Ⅱ will use the recommended dose and dosing regimen from Phase Ⅰb.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Malignant Perivascular Epithelioid Cell Tumor (PEComa)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sirolimus for Injection (Albumin-bound)
Arm Type
Experimental
Arm Description
Sirolimus for injection (Albumin-bound) will be administered intravenously on day 1and day 8 every 21 days (a cycle).
Intervention Type
Drug
Intervention Name(s)
Sirolimus for Injection (Albumin Bound)
Intervention Description
Sirolimus for injection (Albumin-bound), intravenously, once a week, 21 days per cycle (two weeks-on and one week-off)
Primary Outcome Measure Information:
Title
AE and SAE occurrence and frequency in phase Ⅰb
Time Frame
Up to 2 years
Title
Dose-limiting toxicities (DLT)
Time Frame
Cycle 1 (Up to 21 days)
Title
Maximum tolerated dose (MTD)
Time Frame
Cycle 1 (Up to 21 days)
Title
Recommended phase 2 dose (RP2D)
Time Frame
Cycle 1 (Up to 21 days)
Title
Overall response rate (ORR) in phase Ⅱ
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Overall response rate (ORR) in phase Ⅰb
Time Frame
Up to 2 years
Title
Disease Control Rate (DCR)
Time Frame
Up to 2 years
Title
Duration of Response (DOR)
Time Frame
Up to 2 years
Title
Progression-free Survival (PFS)
Time Frame
Up to 2 years
Title
Overall survival (OS)
Time Frame
Up to 2 years
Title
AE and SAE occurrence and frequency in phase Ⅱ
Time Frame
Up to 2 years
Title
Area under the plasma concentration versus time curve (AUC)
Time Frame
Up to 2 years
Title
Peak Plasma Concentration (Cmax)
Time Frame
Up to 2 years
Title
Peak time (Tmax)
Time Frame
Up to 2 years
Title
Terminal half-life (t½)
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged 18 years or older, and Phase Ⅰb: Patients with histologically confirmed diagnosis of advanced soft tissue sarcomas (including malignant PEComa, accounting for at least 1/2) have failed standard treatment (disease progression or relapse or intolerance to chemotherapy, radiotherapy, targeted therapy, etc.) or lack effective treatment; Phase Ⅱ: Patients must have a histologically confirmed diagnosis of malignant PEComa that is either metastatic or locally advanced and for which surgery is not a recommended option. [Malignant PEComas displaying 2 or more of the features of large size (> 5 cm), infiltrative growth, high nuclear grade, cellular necrosis, mitoses ≥1/50 high power field (HPF), or vascular invasion] At least 1 measurable lesion as defined by RECIST 1.1. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Life expectancy >3 months. Patient must have the following biological parameters levels at screening (without blood transfusion, EPO, G-CSF and other medical support within14 days prior to screening tests): Blood tests: Absolute neutrophil count (ANC) ≥1.5 × 10^9/L; Platelet count ≥100 × 10^9/L; Hemoglobin ≥90 g/L; Renal function tests: serum creatinine ≤1.5 x upper limit of normal (ULN); Liver function tests: Total bilirubin ≤1.5 x ULN (Patients with liver metastases, bile duct obstruction, or confirmed Gilbert syndrome: ≤ 3×ULN); AST and ALT ≤2.5 x ULN (≤5 x ULN if attributable to liver metastases); Blood clotting function tests: INR or PT ≤ 1.5 × ULN; APTT≤ 1.5 × ULN; Fasting serum triglycerides<300 mg/dL(3.42 mmol/L), fasting serum cholesterol < 350 mg/dL ( 9.07mmol/L; ). Fasting blood glucose (FPG) < 7.8 mmol/L and HbA1c < 8%. Women of child-bearing potential, or men whose partners are women of childbearing age must agree to use reliable contraceptive methods during the trial period and at least 6 months after the last administration; women of childbearing age must have a negative serum pregnancy test within 7 days prior to the first administration, should not be breast feeding. Patients must give informed consent to the study prior to the trial and voluntarily sign informed consent form. Exclusion Criteria: Anti-tumor therapy such as chemotherapy, radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy within 4 weeks prior to the first dose of study drug, with the following special requirements: Nitrosoureas (eg, carmustine, lomustine, etc.) or mitomycin C within 6 weeks prior to the first dose of study drug; Oral fluorouracils and small molecule targeted drugs within 2 weeks or 5 half-lives (whichever is longer) before the first dose of study drug; Traditional Chinese medicines with anti-tumor indications within 2 weeks prior to the first dose of study drug; Received other unmarketed clinical investigational drug within 4 weeks prior to the first dose of study drug. Major surgical procedures within 4 weeks prior to the first dose of study drug or not fully recovered from any previous invasive procedures. Received systemic glucocorticoids (prednisone > 10 mg/day or equivalent doses) or other immunosuppressive therapy within 2 weeks prior to the first dose of the study drug [with the following exceptions: treatment with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term use of glucocorticoids for prophylaxis (eg, prevention of contrast allergy)]. Infection that required systemic anti-infective therapy (oral or IV) within 2 weeks before enrollment. Inactivated or live attenuated vaccine or novel coronavirus vaccine within 30 days before the first dose. Use of strong inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study drug, or requiring concomitant treatment during the study. History of other malignancies within 5 years prior to the first dose of the study drug, except in the following cases: cured basal cell or squamous cell skin cancer, superficial bladder cancer, prostatic carcinoma in situ, carcinoma in situ of the cervix, breast carcinoma in situ, etc., or locally curable cancer that has been disease-free for 5 years; Liver-directed therapy is required within 2 months of enrollment. Prior treatment with radiotherapy (including radio-labeled spheres and/or cyberknife, hepatic arterial embolization (with or without chemotherapy) or cyrotherapy/ablation) is allowed if these therapies does not affect the areas of measurable disease being used for this protocol. History of serious cardiovascular disease, such as severe heart rhythm or conduction abnormalities (ventricular arrhythmias requiring clinical intervention, grade Ⅱ or Ш atrioventricular block, etc.). History of myocardial infarction, unstable angina, heart failure, New York College of Cardiology (NYHA) grade Ⅱ and above, and coronary artery bypass surgery within 6 months before the first dose of the study drug; Left ventricular ejection fraction (LVEF) < 50%, QTcF > 450 msec (male) or female QTcF > 470 msec (female), etc. Unresolved toxicity from prior anti-tumor therapy greater than Grade 1 as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.(except for alopecia and any other toxicities that have no safety risk judged by the investigator). Known active uncontrolled or symptomatic central nervous system (CNS) metastases, or other evidence of uncontrollable central nervous system metastases or meningeal metastases that not eligible for inclusion determined by the investigator. Hydrothorax, ascites or pericardial effusion with clinical symptoms or required symptomatic treatment. Patients with angiomyolipoma(AML) or lymphangioleiomyomatosis (LAM). History of serious lung disease, such as interstitial lung disease and/or pneumonitis, or pulmonary hypertension, or pre-existing severely impaired lung function. Pre-existing thyroid abnormality is allowed provided thyroid function can be controlled with medication. Known hypersensitivity or intolerance to any ingredient in the study drug. History of autoimmune disease (except tuberous sclerosis), immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency disease, or history of organ transplantation. Active Hepatitis B or Hepatitis C, or active syphilis infection Active Hepatitis B: HBsAg-positive with HBV DNA titer ≥ 1 × 10^3 IU/mL; Patients are eligible for enrollment if they are HBsAg positive with peripheral blood HBV-DNA < 1 × 10^3 IU/mL if, in the opinion of the investigator, the patient's chronic hepatitis B is in a stable phase and does not increase the subject's risk. Active Hepatitis C: HCV antibodies -positive with HCV RNA-positive; Active syphilis infection: Treponema pallidum antibodies (RPR or TRUST)-positive or presence of syphilis infection requiring systemic therapy. Severe concomitant diseases that endanger patient safety, interfere the compliance of the study procedure (such as uncontrollable hypertension, active gastrointestinal bleeding, etc.) or other reasons that make the patient inappropriate for entry into this study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaohui Niu
Phone
+86-1381132522
Email
niuxiaohui@263.net
Facility Information:
Facility Name
Beijing Jishuitan Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaohui Niu
Phone
+861381132522
Email
niuxiaohui@263.net

12. IPD Sharing Statement

Learn more about this trial

A Study of Safety and Efficacy of Sirolimus for Injection (Albumin-bound) in Patients With Advanced Malignant Perivascular Epithelioid Cell Tumor (PEComa)

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