Tolerability and Bioavailability of Utidelone Capsule in Patients With Advanced Solid Tumors

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.

Conditions

• Advanced Solid Tumor

Interventions

DRUG

Utidelone 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.

DRUG

Drug 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.

DRUG

Drug 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.

DRUG

Drug 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.

DRUG

Drug 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.

DRUG

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.

DRUG

Utidelone 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 & Collaborators

• Beijing Biostar Pharmaceuticals Co., Ltd.

  lead INDUSTRY

Principal Investigators

• Binghe Xu, MD, PhD · Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-06-09

Primary Completion

2025-03-09

Completion

2025-04-09

Countries

• China

Study Locations