Trial Title:
Tolerability and Bioavailability of Utidelone Capsule in Patients With Advanced Solid Tumors
NCT ID:
NCT05700084
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Capecitabine
Conditions: Keywords:
Tolerability
Bioavailability
Advanced Solid Tumor
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Crossover Assignment
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Utidelone Capsule (Part 1)
Description:
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.
Arm group label:
Utidelone Capsule (Part 1)
Intervention type:
Drug
Intervention name:
Drug A Utidelone Capsule (Part 2: Group A-B)
Description:
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.
Arm group label:
Utidelone Capsule/Utidelone Injection (Group A-B, Part 2)
Intervention type:
Drug
Intervention name:
Drug A Utidelone Capsule (Part 2: Group B-A)
Description:
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.
Arm group label:
Utidelone Injection/Utidelone Capsule (Group B-A, Part 2)
Intervention type:
Drug
Intervention name:
Drug B Utidelone Injection (Part 2: Group A-B)
Description:
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.
Arm group label:
Utidelone Capsule/Utidelone Injection (Group A-B, Part 2)
Intervention type:
Drug
Intervention name:
Drug B Utidelone Injection (Part 2: Group B-A)
Description:
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.
Arm group label:
Utidelone Injection/Utidelone Capsule (Group B-A, Part 2)
Intervention type:
Drug
Intervention name:
Capecitabine
Description:
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.
Arm group label:
Utidelone Capsule combination with Capecitabine
Intervention type:
Drug
Intervention name:
Utidelone Capsule (Part 3)
Description:
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.
Arm group label:
Utidelone Capsule combination with Capecitabine
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Subjects must meet all of the following criteria to be enrolled into the study:
1. Patients who have fully understood the objectives, content, process of the study and
possible adverse events, voluntarily serves as a subject 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 subjects aged ≥18 and ≤65, Part 3: Male or female
subjects 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 12 weeks 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:
Subjects who fulfill any one of the following exclusion criteria will be excluded from
the study:
1. Patients who have received non-investigational anti-tumor therapies (such as
chemotherapy, radiotherapy, immunotherapy, biological therapy or traditional Chinese
medicine treatment) within 2 weeks prior to study drug administration.
2. Subjects with severe hypersensitivity to castor oil (this criteria is applicable to
Part 2 of the study), and subjects who had hypersensitivity reaction caused by
previous anti-microtubule drugs.
3. Patients with uncontrollable brain metastases (brain metastatic lesion confirmed by
examination within 2 months after radiotherapy or other localized treatment);
patients with uncontrollable bone metastases (patients who have had fracture or have
the risk of fracture in recent days, patients who need surgery or localized
radiotherapy in recent days, patients with other critical conditions)
4. Patients with serious comorbidities, such as severe heart disease, cerebrovascular
disease, uncontrolled diabetes, uncontrolled hypertension, severe infections, active
peptic ulcers, etc.
5. Patients with mental illnesses which are hard to control, patients who lack legal
capacity or have limited legal capacity.
6. Patients with gastrointestinal diseases such as esophageal obstruction, pyloric
obstruction, intestinal obstruction, or who are post-operative of gastrointestinal
resection, or who have difficulty in swallowing due to other factors, interfering
with oral administration and absorption of the drug.
7. Patients with active hepatitis B infections.
8. Patients with peripheral neuropathy grade>1 within 4 weeks prior to enrollment (NCI
CTCAE 5.0).
9. Patients who still experience ≥ Grade 2 acute toxicities caused by previous
anti-tumor therapies (e.g. chemotherapy, radiotherapy, immunotherapy, biological
therapy or TCM treatment) prior to enrollment (NCI-CTCAE 5.0, except alopecia).
10. Patients who have undergone any major surgery or have major trauma within 4 weeks
prior to administration of the investigational product or are expected to undergo
major surgery during the treatment.
11. Patients who have participated in another clinical trial or have received other
investigational treatments within 4 weeks prior to administration of the
investigational product.
12. Patients who, in the opinion of the investigator, are not suitable to participate in
this study.
13. Part 3: other malignant tumors within 5 years before enrollment, excluding cured
cervical carcinoma in situ, skin basal cell carcinoma or skin squamous cell
carcinoma, thyroid papillary carcinoma;
14. Part 3: previous or current capecitabine therapy (except if capecitabine was used in
neoadjuvant/adjuvant therapy and progression occurred > 12 months after completion
of treatment, inclusion was allowed);
15. Part 3: patients with previous fluorouracil medication history with severe allergy
or known dihydropyrimidine dehydrogenase (DPD) deficiency;
16. Part 3: previous or current use of utidelone (including utidelone injection and
utidelone capsule); 17) Part 3: pregnant or lactating patients; 18) Part 3:
uncontrolled pleural effusion, pericardial effusion or ascites (drainage once a
month or more); 19) Part 3: a history of immunodeficiency, including positive HIV
antibody test, other acquired or congenital immunodeficiency diseases, or a history
of organ transplantation.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer Hospital Chinese Academy of Medical Sciences
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Binghe Xu
Start date:
June 9, 2023
Completion date:
April 9, 2025
Lead sponsor:
Agency:
Beijing Biostar Pharmaceuticals Co., Ltd.
Agency class:
Industry
Source:
Beijing Biostar Pharmaceuticals Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05700084
