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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Utidelone Capsule (Part 1) | Experimental | Utidelone Capsule, available as 10 mg/capsule and 15 mg /capsule. Doses between 50 mg/m2/d and 120 mg/m2/d administered orally will be explored. Patients will be dosed for 5/7 consecutive days in a 21 day cycle. |
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| Utidelone Capsule/Utidelone Injection (Group A-B, Part 2) | Experimental | At cycle 0, patients will take Utidelone Capsule in fasted status at 60 mg/m2/d. At cycle 1, patients will be administered Utidelone Injection by iv drip at 30 mg/m2/d. At Cycle 2, patients will take Utidelone Capsule (after meals) at 60 mg/m2/d. |
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| Utidelone Injection/Utidelone Capsule (Group B-A, Part 2) | Experimental | At cycle 0, patients will be administered Utidelone Injection by iv drip at 30 mg/m2/d. At cycle 1, patients will take Utidelone Capsule in fasted status at 60 mg/m2/d. At cycle 2, patients will take Utidelone Capsule (after meals) at 60 mg/m2/d. |
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| Utidelone Capsule combination with Capecitabine | Experimental | Dosage: 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. Capecitabine: 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Utidelone Capsule (Part 1) | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose, MTD | 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). | 8 months |
| Dose-Limiting Toxicity, DLT | 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. | 8 months |
| Objective Response Rate, ORR | To evaluate the objective response rate (ORR) of utidelone capsule combined with capecitabine in the treatment of patients with advanced metastatic breast cancer | 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Bioavailability of Utidelone Capsule | Endpoint indicator: F | 8 months |
| Maximum (or peak) serum concentration-Cmax | Cmax of Utidelone Capsule |
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Inclusion Criteria:
Subjects must meet all of the following criteria to be enrolled into the study:
Exclusion Criteria:
Subjects who fulfill any one of the following exclusion criteria will be excluded from the study:
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| Name | Affiliation | Role |
|---|---|---|
| Binghe Xu, MD, PhD | Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cancer Hospital Chinese Academy of Medical Sciences | Beijing | China | ||||
| The Fifth Medical Center of Chinese PLA General Hospital |
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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.
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| Drug A Utidelone Capsule (Part 2: Group A-B) | Drug | 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. |
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| Drug A Utidelone Capsule (Part 2: Group B-A) | Drug | 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. |
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| Drug B Utidelone Injection (Part 2: Group A-B) | Drug | 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. |
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| Drug B Utidelone Injection (Part 2: Group B-A) | Drug | 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. |
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| Capecitabine | Drug | 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. |
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| Utidelone Capsule (Part 3) | Drug | 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. |
|
| 8 months |
| Time to peak drug concentration-Tmax | Tmax of Utidelone Capsule | 8 months |
| the area under the concentration-time curve from dosing (time 0) to time t-AUC0-t | the AUC0-t of Utidelone Capsule | 8 months |
| the time required for plasma concentration of a drug to decrease by 50%-t1/2 | the t1/2 of Utidelone Capsule | 8 months |
| Objective Response Rate-ORR | The percentage of patients who have a partial response or complete response to the treatment within a certain period of time. | 12 months |
| Treatment-related Adverse Event-TRAE | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | 12 months |
| Progression-Free Survival, PFS | To evaluate the Progression-Free Survival (PFS) of eutidrone capsules combined with capecitabine in the treatment of patients with advanced metastatic breast cancer. | 6 weeks |
| Beijing |
| China |
| Sichuan Cancer Hospital | Chengdu | China |
| Sun Yat-sen University Cancer Center | Guangzhou | China |
| Cancer Hospital of Shandong First Medical University | Jinan | China |
| Renji Hospital, Shanghai Jiao Tong University School of Medicine | Shanghai | China |
| LiaoNing Cancer Hospital&Institute | Shenyang | China |
| The Fourth Hospital of Hebei Medical University | Shijiazhuang | China |
| Union Hospital, Tongji Medical College, Huazhong University of Science and Technology | Wuhan | China |
| The First Affiliated Hospital of XI'an JiaoTong University | Xi'an | China |
| ID | Term |
|---|---|
| D000069287 | Capecitabine |
| ID | Term |
|---|---|
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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