Advanced Solid Tumor
Conditions
Keywords
Tolerability, Bioavailability, Advanced Solid Tumor
Brief summary
This study has three parts. Part 1 is a dose-escalation trial, Part 2 is a pharmacokinetic comparison and food effect study, and Part 3 is extended trial of combination of utidelone capsule and capecitabine. The primary objectives are 1. To evaluate the safety and tolerability of utidelone capsules in patients with advanced solid tumors and to determine the Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT). 2. To evaluate the objective response rate in patients with advanced metastatic breast cancer treated with the combination of utidelone capsule and capecitabine. The secondary objectives are: 1. to evaluate the absolute bioavailability of utidelone capsules relative to utidelone injection; 2. to evaluate the pharmacokinetic profile of utidelone capsules in patients with advanced solid tumors; 3. to preliminarily evaluate the efficacy and safety of utidelone capsules in patients with advanced solid tumors; and 4. to recommend doses and dosing regimens for subsequent clinical trials. 5. To evaluate the Progression-Free Survival (PFS), safety and pharmacokinetics of utidelone capsule combined with capecitabine in the treatment of patients with advanced metastatic breast cancer.
Detailed description
Part 1 is a dose-escalation trial, and it's an open design; Part 2 is a pharmacokinetic comparison and food effect study, and it's an open, controlled study;Part 3: Extended trial of combination of utidelone capsule and capecitabine.
Interventions
DRUGUtidelone Capsule (Part 1)
At least 3 dose cohorts are planned, and 14-26 cases are expected. Cohort 1: 2 cases are planned, and the subjects will receive Utidelone Capsule at a dose of 50 mg/m2/d for 5 days. Other dose-escalation cohorts: 3-6 cases are planned in each cohort, following the 3 + 3 design. The subjects in these cohorts will receive Utidelone Capsule at 75 mg/m2/d for 5 days, 100 mg/m2/d for 5 days, 100 mg/m2/d for 7 days, and 120 mg/m2/d for 7 days, in a 21-day cycle respectively.
DRUGDrug A Utidelone Capsule (Part 2: Group A-B)
Utidelone Capsule at Part 2 in Group A-B will be administered at 60 mg/m2/d. At Cycle 0, on day 1, all patients will receive the drug in fasted status with a glass (approximately 240 ml) of warm water (2 h of fasting before administration; 2 h of fasting after administration). At Cycle 2, subjects will receive the drug after meals on days 1-5 (high-fat meal, drug taken 30 min after the meal; 2 h fasting after administration). Subjects will receive the drug on day 1-5 with 21 days as a cycle. For the subsequent treatment period, there is no special requirements for food. Subjects will receive the drug on day 1-5 with 21 days as a cycle.
DRUGDrug A Utidelone Capsule (Part 2: Group B-A)
Utidelone Capsule at Part 2 in Group B-A will be administered at 60 mg/m2/d. At Cycle 1, on day 1-5, all patients will receive the drug in fasted status with a glass (approximately 240 ml) of warm water (2 h of fasting before administration; 2 h of fasting after administration), with 21 days as a cycle. At Cycle 2, subjects will receive the drug after meals on days 1-5 (high-fat meal, drug taken 30 min after the meal; 2 h fasting after administration), with 21 days as a cycle. For the subsequent treatment period, there is no special requirements for food. Subjects will receive the drug on day 1-5 with 21 days as a cycle.
DRUGDrug B Utidelone Injection (Part 2: Group A-B)
Utidelone Injection at Part 2 in Group A-B will be administered at 30 mg/m2/d in 250 mL normal saline, intravenous drip over1.5 h. For Cycle 1, subjects will be administered Utidelone Injection on day 1-5 with 21 days as a cycle.
DRUGDrug B Utidelone Injection (Part 2: Group B-A)
Utidelone Injection at Part 2 in Group B-A will be administered at 30 mg/m2/d in 250 mL normal saline, intravenous drip over1.5 h. For Cycle 0, all patients will be administered Utidelone Injection on day 1, with 21 days as a cycle.
DRUGCapecitabine
1000mg/m2, twice a day (daily dose 2000mg/m2), once in the morning and once in the evening, taken orally within 30 minutes after meals. It is administered continuously for 14 days from day 1 to day 14, with a 21 day treatment cycle.
DRUGUtidelone Capsule (Part 3)
Utidelone capsule: 60 mg/m2/d, administered once a day on an empty stomach, continuously for 5 days from day 1 to day 5, with a treatment cycle of 21 days.
Sponsors
Beijing Biostar Pharmaceuticals Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Study design: Part 1 is a dose-escalation trial, and it's an open design; Part 2 is for pharmacokinetic comparison and food effect study, and it's an open, controlled design. Part 3 is expansion test of utidelone capsule combined with capecitabine. In the Part 1 dose-escalation trial, there is no control; in the Part 2 pharmacokinetic comparison and food effect study, utidelone injection is chosen as the control drug in Cycle 0 and 1; in Cycle 2 day1, high-fat postprandial dosing is served as the control.Part 3: expansion test of utidelone capsule combined with capecitabine dosage administered.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
All inclusion criteria must be met for enrollment: 1. Patients who have fully understood the objectives, content, process of the study and possible adverse events, voluntarily serves as a participant and signs the informed consent form. 2. Part 1 and Part 2: Patients with definitive histopathological diagnosis of advanced solid tumors. Part 3: Patients were diagnosed with advanced metastatic breast cancer by pathology and/or cytology. 3. Part 1 and Part 2: Male or female participants aged ≥18 and ≤65, Part 3: Male or female participants aged ≥18 and ≤70, with ECOG performance status scored 0-1. 4. Expected survival time ≥ 12 weeks; 5. At least one measurable lesion present according to RECIST 1.1 criteria. 6. Baseline routine blood tests within 1 week prior to enrollment is normal (not received blood transfusions or hematopoietic-stimulating factors within 14 days), with CTCAE grade ≤1 (based on normal values at each site's laboratory): a) Neutrophil count (ANC) ≥ 1.5 × 109/L; b) platelet count (PLT ) ≥ 100 × 109/L; c) Hemoglobin ≥9.0 g/dL. 7. Liver and kidney function test results are normal within 1 week prior to enrollment, with CTCAE grade ≤1 (based on normal values at each site's laboratory): a) Total bilirubin (TBIL) ≤ 1.5× the upper limit of normal value (ULN); b) Serum Glutamic Pyruvic Transaminase/Alanine Aminotransferease (SGPT /ALT) ≤ 2.5× ULN (Part 3 allowed ≤5×ULN in patients with liver metastases); c) Serum Glutamic-oxaloacetic Transaminase/Aspartate Aminotransferase (SGOT /AST) ≤ 2.5× ULN (Part 3 allowed ≤5×ULN in patients with liver metastases); d) Creatinine clearance (Ccr) ≥60 ml/min. 8. Patients with no functional disorders of major organs. 9. Fertile males and females of childbearing potential must agree to use effective contraception (so do their partners, using hormonal or barrier contraception, or abstinence) during the study and within at least 6 months after the last dose. The blood or urine pregnancy test for female patients of childbearing potential prior to enrollment must be negative. 10. Part 3: breast cancer patients who had received ≤4 previous chemotherapy regimens (adjuvant chemotherapy/neoadjuvant chemotherapy was considered as one chemotherapy regimen); 11. Part 3: history of prior treatment with at least one anthracycline or one taxane as neoadjuvant/adjuvant or advance therapy or both.
Exclusion criteria
Meet any
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose, MTD | 8 months | The maximum tolerated dose (MTD) is defined as the highest dose tested in which none or only one patient experienced DLT attributable to the study drug(s), when 6 patients were treated at that dose and are evaluable for toxicity. The MTD is one dose level below the lowest dose tested in which 2 or more patients experienced DLT attributable to the study drug(s). |
| Dose-Limiting Toxicity, DLT | 8 months | DLT is observed during Cycle 1 in the dose escalation trial. Any toxicity meeting the criteria outlined in the protocol, at least possibly related to study drug (i.e. definitely, probably, or possibly attributed), will be considered a DLT. |
| Objective Response Rate, ORR | 6 weeks | To evaluate the objective response rate (ORR) of utidelone capsule combined with capecitabine in the treatment of patients with advanced metastatic breast cancer |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bioavailability of Utidelone Capsule | 8 months | Endpoint indicator: F |
| Maximum (or peak) serum concentration-Cmax | 8 months | Cmax of Utidelone Capsule |
| Time to peak drug concentration-Tmax | 8 months | Tmax of Utidelone Capsule |
| the area under the concentration-time curve from dosing (time 0) to time t-AUC0-t | 8 months | the AUC0-t of Utidelone Capsule |
| the time required for plasma concentration of a drug to decrease by 50%-t1/2 | 8 months | the t1/2 of Utidelone Capsule |
| Objective Response Rate-ORR | 12 months | The percentage of patients who have a partial response or complete response to the treatment within a certain period of time. |
| Treatment-related Adverse Event-TRAE | 12 months | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |
| Progression-Free Survival, PFS | 6 weeks | To evaluate the Progression-Free Survival (PFS) of eutidrone capsules combined with capecitabine in the treatment of patients with advanced metastatic breast cancer. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORBinghe Xu, MD, PhD
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed