Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Docetaxel for Injection (Albumin-bound) in Different Dose Regimens in Patients With Advanced Solid Tumors: An Open-label, Multicenter, Phase 1b Study
Overview
- Phase
- Phase 1
- Intervention
- Albumin-bound docetaxel
- Conditions
- Advanced Solid Tumors
- Sponsor
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Enrollment
- 144
- Locations
- 1
- Primary Endpoint
- The maximum tolerated dose (MTD) (if available) and recommended phase 2 dose (RP2D) in stage I
- Last Updated
- 4 years ago
Overview
Brief Summary
The aim of this study is designed to evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of docetaxel for injection (albumin-bound) in different dose regimens in patients with advanced solid tumors.
Detailed Description
This study will be conducted in two stages. The first stage (Stage I) is a dose-escalation study. A classic 3+3 design will be used to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D). Patients will receive the docetaxel for injection (albumin-bound) until disease progression, or intolerable toxicity, or other reasons for termination of the study. All dose-escalation decisions will be based on the safety data generated from the current highest dose group. In the cohort-expansion study (Stage Ⅱ), patients with a potential to have better response to the study drug will be recruited. Patients will receive the docetaxel for injection (albumin-bound) at the recommended phase 2 dose (RP2D) and follow the treatment regimen established in Stage I.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients aged ≥18, ≤75 years (subject to the date when the informed consent form is signed) and voluntarily signed the informed consent form.
- •Histologically or cytologically confirmed diagnosis of advanced or metastatic solid tumors, for which standard therapy either does not exist or has proven to be ineffective, intolerable or unacceptable for the patient.
- •At least one measurable lesion according to RECISTv1.
- •Patients with Eastern Cooperative Oncology Group (ECOG) performance status score of 0-
- •Patients with estimated survival time of ≥ 3 months.
- •Main organ function meets the following criteria within 7 days before treatment (no medical supportive treatments such as blood component transfusion, human granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), interleukin-11, and erythropoietin (EPO) within 2 weeks before baseline examination):
- •Absolute neutrophil count ≥1.5×10\^9/L; Platelets ≥100×10\^9/L; Hemoglobin ≥90 g/L or ≥5.6 mmol/L; Serum creatinine ≤ 1.5×ULN or creatinine clearance rate ≥ 50 mL/min; Liver function: total bilirubin≤ 1.0 × ULN, ≤ 1.5 × ULN for patients with liver metastasis or liver cancer; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN, ≤ 2.5 × ULN for patients with liver metastasis or liver cancer.
- •Fertile patients must use contraceptive measures (such as intrauterine device \[IUD\], contraceptive pill or condom) during the study period and within 6 months after the end of the study, and men should avoid sperm donation; Women of childbearing age must have negative serum pregnancy test within 7 days before study enrollment, and must be non-lactating women.
Exclusion Criteria
- •Patients with central nervous system metastasis or meningeal metastasis, accompanied by the following conditions:
- •Patients with clinical symptoms related to central nervous system metastasis or meningeal metastasis;
- •New lesions in the brain or progression of the original lesions on imaging from the end of brain radiotherapy or surgery to the first administration;
- •Central nervous system metastasis with cortical alcohols, radiotherapy, dehydration drugs and other drugs for symptoms control within the last two weeks;
- •Patients has brain stem (midbrain, pons, medulla oblongata) metastasis;
- •Other evidence shows that the patient's central nervous system metastasis or meningeal metastasis has not been controlled, which is not suitable for inclusion according to the judgment of the researcher.
- •Known human immunodeficiency virus (HIV) test positive or known history of acquired immunodeficiency syndrome (AIDS), history of organ transplantation, history of serious autoimmune diseases judged by the researchers to be unsuitable for inclusion.
- •HCV antibody (+) or active hepatitis B (HBsAg positive and HBV DNA \> 500 IU/mL) and uncontrolled active infection (those who must receive systematic anti infection treatment, or those with unexplained body temperature \> 38 ℃ (axillary temperature) before administration).
- •Patients have a history of serious cardiovascular diseases, including but not limited to:
- •Severe heart rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention and third-degree atrioventricular block;
Arms & Interventions
Docetaxel for Injection-qw 3/4 regimen
Docetaxel for Injection (Albumin-bound) will be administrated once every week in the first three weeks (Day 1, 8 and 15) in every 28-day cycle, starting at a dose of 30 mg/m\^2.
Intervention: Albumin-bound docetaxel
Docetaxel for Injection-q2w 2/4 regimen
Docetaxel for Injection (Albumin-bound) will be administrated once every week every other week (Day 1 and 15) in every 28-day cycle, starting at a dose of 50 mg/m\^2.
Intervention: Albumin-bound docetaxel
Docetaxel for Injection-qw 2/3 regimen
Docetaxel for Injection (Albumin-bound) will be administrated once every week in the first two weeks (Day 1 and 8) in every 21-day cycle, starting at a dose of 30 mg/m\^2.
Intervention: Albumin-bound docetaxel
Outcomes
Primary Outcomes
The maximum tolerated dose (MTD) (if available) and recommended phase 2 dose (RP2D) in stage I
Time Frame: At the end of Cycle 1 (each cycle is 28 or 21 days)
The maximum tolerated dose
Overall response rate (ORR) in stage Ⅱ
Time Frame: Up to approximately 2 years
Objective response rate
Progression-free survival (PFS) in stage Ⅱ
Time Frame: Up to approximately 2 years
Progression-free survival
Disease control rate (DCR) in stage Ⅱ
Time Frame: Up to approximately 2 years
Disease control rate
Duration of response (DOR) in stage Ⅱ
Time Frame: Up to approximately 2 years
Duration of response
The occurrence and frequency of adverse events and serious adverse events
Time Frame: Up to approximately 2 years
Incidence of adverse events and serious adverse events
Secondary Outcomes
- Maximum plasma concentration (Cmax)(At the end of Cycle 1 (each cycle is 28 or 21 days))
- Time to maximum plasma concentration (Tmax)(At the end of Cycle 1 (each cycle is 28 or 21 days))
- Area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC0-last)(At the end of Cycle 1 (each cycle is 28 or 21 days))
- Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)(At the end of Cycle 1 (each cycle is 28 or 21 days))
- Plasma half-life (t½)(At the end of Cycle 1 (each cycle is 28 or 21 days))
- Volume of distribution (Vd)(At the end of Cycle 1 (each cycle is 28 or 21 days))
- Plasma clearance (CL)(At the end of Cycle 1 (each cycle is 28 or 21 days))
- Cumulative urinary excretion rate of docetaxel prototypes(At the end of Cycle 1 (each cycle is 28 or 21 days))
- Preliminary identification of major metabolites in plasma and urine samples(At the end of Cycle 1 (each cycle is 28 or 21 days))